%0 Journal Article %~ PubMed %A Hong, Angela M %A Martin, Andrew %A Chatfield, Mark %A Jones, Deanna %A Zhang, Mei %A Armstrong, Bruce %A Lee, C Soon %A Harnett, Gerald %A Milross, Christopher %A Clark, Jonathan %A Elliott, Michael %A Smee, Robert %A Corry, June %A Liu, Chen %A Porceddu, Sandro %A Rees, Guy %A Rose, Barbara %T Human papillomavirus, smoking status and outcomes in tonsillar squamous cell carcinoma. %B International Journal of Cancer %D 2013 %C United States %I John Wiley & Sons, Inc. %V 132 %N 12 %P 2748-2754 %@ 1097-0215 %X %Z FOR Codes: 111201 %0 Journal Article %~ PubMed %A Hong, Angela %A Zhang, Mei %A Veillard, Anne-Sophie %A Jahanbani, Jahanfar %A Lee, C Soon %A Jones, Deanna %A Harnett, Gerald %A Clark, Jonathan %A Elliott, Michael %A Milross, Chris %A Rose, Barbara %T The prognostic significance of hypoxia inducing factor 1-α in oropharyngeal cancer in relation to human papillomavirus status. %B Oral Oncology %D 2013 %C United Kingdom %I Pergamon %V 49 %N 4 %P 354-359 %@ 1368-8375 %X %Z FOR Codes: 1112 %0 Journal Article %~ PubMed %A Tsang, Julia Y S %A Mendoza, Paulo %A Putti, Thomas C %A Karim, Rooshdiya Z %A Scolyer, Richard A %A Lee, C Soon %A Pang, Amy L M %A Tse, Gary M %T E-cadherin expression in the epithelial components of mammary phyllodes tumors. %B Human Pathology %D 2012 %C United States %I W.B. Saunders Co. %V 43 %N 12 %P 2117-2123 %@ 1532-8392 %X %Z FOR Codes: 110316 %0 Journal Article %~ PubMed %A Bennett, Nigel C %A Hooper, John D %A Lambie, Duncan %A Lee, Cheok S %A Yang, Tao %A Vesey, David A %A Samaratunga, Hemamali %A Johnson, David W %A Gobe, Glenda C %T Evidence for steroidogenic potential in human prostate cell lines and tissues. %B American Journal of Pathology %D 2012 %C United States %I Elsevier Inc. %V 181 %N 3 %P 1078-1087 %@ 0002-9440 %X %Z FOR Codes: 111201 %0 Journal Article %~ PubMed %A Tsang, Julia Y S %A Mendoza, Paulo %A Lam, Christopher C F %A Yu, Alex M C %A Putti, Thomas C %A Karim, Rooshdiya Z %A Scolyer, Richard A %A Lee, Cheok Soon %A Tan, Puay Hoon %A Tse, Gary M %T Involvement of α- and β-catenins and E-cadherin in the development of mammary phyllodes tumours. %B Histopathology %D 2012 %C United Kingdom %I Wiley-Blackwell Publishing Ltd. %V 61 %N 4 %P 667-674 %@ 0309-0167 %X Tsang J Y S, Mendoza P, Lam C C F, Yu A M C, Putti T C, Karim R Z, Scolyer R A, Lee C S, Tan P H & Tse G M (2012) Histopathology Involvement of ?- and ?-catenins and E-cadherin in the development of mammary phyllodes tumours Aims:? Phyllodes tumours (PT) are rare but clinically important fibroepithelial tumours of the breast. ?-Catenin, a key component in Wnt signalling, has been shown to be important in the development of PT. It also functions as a component of the cadherin complex, which may therefore be implicated in PT pathogenesis. By assessing stromal ?-catenin, ?-catenin and E-cadherin expression in 158 PT cases using immunohistochemistry and examining associations with clinicopathological features, we aimed to determine the role of these proteins in PT pathogenesis. Methods and results:? Cytoplasmic ?-catenin correlated with ?-catenin expression. A significantly higher expression of both markers was observed in borderline than in benign PT (P?=?0.003 and <0.001, respectively), but a lower level was found in malignant PT. Cytoplasmic E-cadherin expression was significantly higher in borderline and malignant than in benign PT (P?=?0.001 and 0.012, respectively), but was not correlated with other markers. Both E-cadherin and ?-catenin showed stronger correlations with histological parameters than ?-catenin. ?-Catenin showed a significant correlation with recurrence (P?=?0.005 and 0.016, respectively). Conclusions:? ?- and ?-catenins may be important in the early stages of PT development, while E-cadherin may be required for malignant development. The correlation of ?-catenin expression with tumour recurrence may be relevant in predicting PT behaviour. %Z FOR Codes: 111201 %0 Journal Article %~ PubMed %A Killingsworth, Murray C %A Lai, Ken %A Wu, Xiaojuan %A Yong, Jim L C %A Lee, C Soon %T Quantum Dot Immunocytochemical Localization of Somatostatin in Somatostatinoma by Widefield Epifluorescence, Super-resolution Light, and Immunoelectron Microscopy. %B Journal of Histochemistry and Cytochemistry %D 2012 %C United States %I Sage Publications, Inc. %V 60 %N 11 %P 832-843 %@ 1551-5044 %X %Z FOR Codes: 601 %0 Journal Article %~ PubMed %A Shin, Joo-Shik %A Foo, Terence %A Hong, Angela %A Zhang, Mei %A Lum, Trina %A Solomon, Michael J %A Lee, C Soon %T Telomerase expression as a predictive marker of radiotherapy response in rectal cancer. %B Pathology %D 2012 %C United Kingdom, Australia %I Informa Healthcare %V 44 %N 3 %P 209-215 %@ 0031-3025 %X To investigate telomerase as a predictive marker of radiotherapy response in rectal cancer. %Z FOR Codes: 111201 %0 Journal Article %~ PubMed %A Shin, Joo-Shik %A Jalaludin, Bin %A Solomon, Michael %A Hong, Angela %A Lee, C Soon %T Histopathological regression grading versus staging of rectal cancer following radiotherapy. %B Pathology %D 2011 %C United Kingdom, Australia %I Informa Healthcare %V 43 %N 1 %P 24-30 %@ 0031-3025 %X To compare histological grading of rectal cancer radiotherapy response with pathological staging as a prognostic indicator. %Z FOR Codes: 110316 %0 Journal Article %~ PubMed %A Yip, Po Yee %A Kench, James G %A Rasiah, Krishan K %A Benito, Ruth Pe %A Lee, C-Soon %A Stricker, Phillip D %A Henshall, Susan M %A Sutherland, Robert L %A Horvath, Lisa G %T Low AZGP1 expression predicts for recurrence in margin-positive, localized prostate cancer. %B The Prostate %D 2011 %C United States %I John Wiley & Sons, Inc. %V 71 %N 15 %P 1638-45 %@ 1097-0045 %X Men with positive margins after radical prostatectomy (RP) for localized prostate cancer (PC) have a 40-50% biochemical relapse rate at 5 years. Adjuvant radiotherapy improves biochemical progression-free and overall survival in men with positive margins, but is associated with increased toxicity. There is an urgent need to identify new prognostic markers to define the group of patients who would benefit from multimodality therapy. %Z FOR Codes: 111202 110312 %0 Journal Article %~ PubMed %A Huang, Katie T %A Dobrovic, Alexander %A Yan, Max %A Karim, Rooshdiya Z %A Lee, C Soon %A Lakhani, Sunil R %A Fox, Stephen B %T DNA methylation profiling of phyllodes and fibroadenoma tumours of the breast. %B Breast Cancer Research and Treatment %D 2010 %C United States %I Springer New York LLC %V 124 %N 2 %P 555-565 %@ 0167-6806 %X Phyllodes tumours and cellular fibroadenomas are both fibroepithelial tumours of the breast. Phyllodes tumours, unlike fibroadenomas, have the ability to recur and metastasise. Although these lesions can be distinguished by their stromal cellularity, mitotic index, presence or absence of stromal overgrowth and cellular atypia, there is overlap and not infrequently a definitive diagnosis cannot be made, particularly on biopsy. We sought to evaluate whether DNA promoter methylation profiling using selected genes known to be methylated in cancer would allow us to learn more about the biology of these tumours, and whether it could identify methylation markers that could differentiate phyllodes tumours from fibroadenomas and/or distinguish phyllodes tumours of different grades. Methylation-sensitive high resolution melting (MS-HRM) was used to screen promoter DNA methylation changes in 86 phyllodes tumours (15 benign, 28 borderline, 43 malignant) and 26 fibroadenomas. A panel of 11 genes (RASSF1A, TWIST1, APC, WIF1, MGMT, MAL, RAR?, CDKN2A, CDH1, TP73 and MLH1) was tested. Methylation status was correlated with histology and with clinicopathological parameters. Five of the gene promoters showed some methylation in a proportion of phyllodes tumours; RASSF1A, 45.3%; TWIST1, 10.7%; APC, 4.1%; WIF1, 2.9% and MGMT, 1.3%. Only two genes showed any methylation in fibroadenomas usually at background levels; RASSF1A, 53.8% and MGMT, 8.3%. No CDKN2A methylation was observed in either tumour type, contrary to previous reports. Overall, the methylation patterns differed little from that which might be seen in normal cells. However, significant levels of methylation of RASSF1A (24.4%) and TWIST1 (7.1%) was observed in some phyllodes tumours. Elevated RASSF1A and/or TWIST1 methylation was significantly associated with phyllodes tumours compared with fibroadenomas (P = 0.02), TWIST1 methylation correlated with increasing malignancy in phyllodes tumours (P < 0.001). In conclusion, assessment of methylation of RASSF1A and TWIST1 may aid in the diagnosis of phyllodes tumours. The absence of frequent methylation in fibroadenomas supports a non-neoplastic origin. %Z FOR Codes: 111203 %0 Journal Article %~ PubMed %A Zardawi, Sarah J %A Zardawi, Ibrahim %A McNeil, Catriona M %A Millar, Ewan K A %A McLeod, Duncan %A Morey, Adrienne L %A Crea, Paul %A Murphy, Niamh C %A Pinese, Mark %A Lopez-Knowles, Elena %A Oakes, Samantha R %A Ormandy, Christopher J %A Qiu, Min Ru %A Hamilton, Anne %A Spillane, Andrew %A Soon Lee, Cheok %A Sutherland, Robert L %A Musgrove, Elizabeth A %A O'Toole, Sandra A %T High Notch1 protein expression is an early event in breast cancer development and is associated with the HER-2 molecular subtype. %B Histopathology %D 2010 %C United Kingdom %I Wiley-Blackwell Publishing Ltd. %V 56 %N 3 %P 286-296 %@ 0309-0167 %X AIMS: Activation of Notch signalling results in hyperplasia and tumorigenesis in murine mammary epithelium. However, there is little information regarding the expression of Notch1 in premalignant lesions and early breast cancer. We investigated expression of Notch1 in breast cancer development and its association with molecular subtypes. METHODS AND RESULTS: Immunohistochemical expression of Notch1 was determined in a murine model of mammary carcinogenesis and in breast tissue from two cohorts of breast cancer patients, the first (n=222) comprising a histological progression series and the second an outcome series of 228 patients with operable invasive ductal carcinoma. Enhanced expression of Notch1 protein was an early event in both murine and human breast cancer development with progressive increases in expression with the development of hyperplasia and malignancy. High Notch1 was not prognostic in the outcome cohort. There was, however, a highly significant association of high Notch1 protein with the HER-2 molecular subtype of breast cancer (P=0.008). CONCLUSIONS: These data demonstrate that aberrant Notch regulation is an early event in mammary carcinogenesis and is associated with the HER-2 molecular subtype of breast cancer, and suggest the Notch signalling pathway may be a potential therapeutic target worthy of further investigation. %Z FOR Codes: 111201 %0 Journal Article %~ PubMed %A Murphy, Niamh C %A Biankin, Andrew V %A Millar, Ewan K A %A McNeil, Catriona M %A O'Toole, Sandra A %A Segara, Davendra %A Crea, Paul %A Olayioye, Monilola A %A Lee, C Soon %A Fox, Stephen B %A Morey, Adrienne L %A Christie, Michael %A Musgrove, Elizabeth A %A Daly, Roger J %A Lindeman, Geoffrey J %A Henshall, Susan M %A Visvader, Jane E %A Sutherland, Robert L %T Loss of STARD10 expression identifies a group of poor prognosis breast cancers independent of HER2/Neu and triple negative status. %B International journal of cancer. Journal international du cancer %D 2010 %C United States, Switz %I John Wiley & Sons, Inc. %V 126 %N 6 %P 1445-53 %@ 1097-0215 %X The phospholipid transfer protein STARD10 cooperates with c-erbB signaling and is overexpressed in Neu/ErbB2 breast cancers. We investigated if STARD10 expression provides additional prognostic information to HER2/neu status in primary breast cancer. A published gene expression dataset was used to determine relationships between STARD10 and HER2 mRNA levels and patient outcome. The central findings were independently validated by immunohistochemistry in a retrospective cohort of 222 patients with breast cancer with a median follow-up of 64 months. Kaplan-Meier and Cox proportional hazards analyses were used for univariate and multivariate analyses. Patients with low STARD10 or high HER2 tumor mRNA levels formed discrete groups each associated with a poor disease-specific survival (p = 0.0001 and p = 0.0058, respectively). In the immunohistochemical study low/absent STARD10 expression i.e. < or = 10% positive cells was observed in 24 of 222 (11%) tumors. In a univariate model, low/absent STARD10 expression was significantly associated with decreased patient survival (p = 0.0008). In multivariate analyses incorporating tumor size, tumor grade, lymph node status, ER, PR and HER2 status, low STARD10 expression was an independent predictor of death from breast cancer (HR: 2.56 (95% CI: 1.27-5.18), p = 0.0086). Furthermore, low/absent STARD10 expression, HER2 amplification and triple negative status were independent prognostic variables. Loss of STARD10 expression may provide an additional marker of poor outcome in breast cancer identifying a subgroup of patients with a particularly adverse prognosis, which is independent of HER2 amplification and the triple negative phenotype. %Z FOR Codes: 111299 %0 Journal Article %~ PubMed %A Hong, Angela %A Dobbins, Timothy %A Lee, C Soon %A Jones, Deanna %A Jackson, Elise %A Clark, Jonathan %A Armstrong, Bruce %A Harnett, Gerald %A Milross, Christopher %A O'Brien, Christopher %A Rose, Barbara %T Relationships between epidermal growth factor receptor expression and human papillomavirus status as markers of prognosis in oropharyngeal cancer. %B European journal of cancer (Oxford, England : 1990) %D 2010 %C United Kingdom, Belg %I Pergamon %V 46 %N 11 %P 2088-96 %@ 1879-0852 %X This study examines the prognostic significance of epidermal growth factor receptor (EGFR) expression in relation to human papillomavirus (HPV) status in oropharyngeal squamous cell carcinoma (SCC). %Z FOR Codes: 111204 %0 Journal Article %~ PubMed %A Hong, Angela M %A Grulich, Andrew E %A Jones, Deanna %A Lee, C Soon %A Garland, Suzanne M %A Dobbins, Timothy A %A Clark, Jonathan R %A Harnett, Gerald B %A Milross, Christopher G %A O'Brien, Christopher J %A Rose, Barbara R %T Squamous cell carcinoma of the oropharynx in Australian males induced by human papillomavirus vaccine targets. %B Vaccine %D 2010 %C United Kingdom %I Elsevier Ltd %V 28 %N 19 %P 3269-3272 %@ 0264-410X %X This study provides Australian data on the incidence of human papillomavirus (HPV)-related oropharyngeal cancer to aid the debate on extending the HPV vaccination programme to males. The HPV status for 302 oropharyngeal cancers diagnosed between 1987 and 2006 was determined by HPV E6-targeted multiplex real-time PCR/p16 immunohistochemistry. The overall HPV-positivity rate was 36% (94% types 16 and 18). HPV-related cancer increased from 19% (1987-1990) to 47% (2001-2005). HPV data used in conjunction with Australian cancer incidence data 2001-2005 showed that 1.56 cases of oropharyngeal cancer per 100,000 males per year were associated with HPV types targeted by the vaccine. Vaccinating males may substantially reduce the burden of oropharyngeal cancer in Australia. %Z FOR Codes: 111201 %0 Journal Article %~ PubMed %A Sharma, Sowmya %A Shin, Joo-Shik %A Grimshaw, Matthew %A Clarke, Raymond A %A Lee, C Soon %T The senescence pathway in prostatic carcinogenesis. %B Pathology %D 2010 %C United Kingdom, Australia %I Informa Healthcare %V 42 %N 6 %P 507-511 %@ 0031-3025 %X Prostate cancer is a disease of the old and with increasing life expectancy, its incidence will continue to increase in the future. Control of prostate cancer has involved androgen ablation as a routine form of therapy. However, after an initial response, therapy-resistant clones can appear and result in cancer progression and metastasis with high mortality. The precise mechanisms for the development of androgen resistance are yet uncertain. It appears to be multi-factorial and relates not only to newly acquired genomic capabilities of the cancer cells but also to their interaction with their microenvironment. Overcoming cellular senescence is essential for oncogenesis. Although it seems to be a protective response for normal cells to avoid malignant transformation, senescence can on the other hand promote tumour progression. Interaction of senescent cancer cells with their microenvironment may be the key link to survival or regression of neoplastic cells. Hence, there is speculation that senescence may be a useful new target for therapy in the future. We review the role of senescence in prostate cancer and the effect of tumour microenvironment on androgen resistance. %Z FOR Codes: 111201 %0 Journal Article %~ PubMed %A Hong, Angela M %A Dobbins, Timothy A %A Lee, C Soon %A Jones, Deanna %A Fei, Jimin %A Clark, Jonathan R %A Armstrong, Bruce K %A Harnett, Gerald B %A Milross, Christopher G %A Tran, Nham %A Peculis, Luiza D %A Ng, Cecilia %A Milne, Andrew G %A Loo, Christine %A Hughes, Louise J %A Forstner, Dion F %A O'Brien, Christopher J %A Rose, Barbara R %T Use of cyclin D1 in conjunction with human papillomavirus status to predict outcome in oropharyngeal cancer. %B International journal of cancer. Journal international du cancer %D 2010 %C United States, Switz %I John Wiley & Sons, Inc. %V 128 %N %P 1532-45 %@ 1097-0215 %X There is increasing use of multiple molecular markers to predict prognosis in human cancer. Our aim was to examine the prognostic significance of cyclin D1 and retinoblastoma (pRb) expression in association with human papillomavirus (HPV) status in oropharyngeal squamous cell carcinoma. Clinical records and specimens of 226 patients with follow-up from 1 to 235 months postdiagnosis were retrieved. Tumor HPV status was determined by HPV E6-targeted multiplex real-time PCR/p16 semiquantitative immunohistochemistry and cyclin D1 and pRb expression by semiquantitative immunohistochemistry. Determinants of recurrence and mortality hazards were modeled using Cox regression with censoring at dates of last follow-up. The HPV-positivity rate was 37% (91% type 16). HPV was a predictor of recurrence, an event (recurrence or death) and death after adjustment for clinicopathological variables. There were inverse relationships between HPV status and cyclin D1 and pRb. On univariate analysis, cyclin D1 predicted locoregional recurrence, event and death and pRb predicted event and death. Within the HPV-positive group, after adjusting for clinicopathological factors, patients with cyclin D1-positive cancers had up to a eightfold increased risk of poor outcome relative to those with cyclin D1-negative tumors. However, within the HPV-negative group, there was only a very small adjusted increased risk. A combination of pRb and HPV did not provide additional prognostic information. Our data provide the first evidence that a combination of HPV and cyclin D1 provides more prognostic information in oropharyngeal cancer than HPV alone. If findings are confirmed, treatment based on HPV and cyclin D1 may improve outcomes. %Z FOR Codes: 604 304 601 %0 Journal Article %~ PubMed %A Karim, Rooshdiya Z %A Gerega, Sebastien K %A Yang, Y H %A Spillane, Andrew %A Carmalt, Hugh %A Scolyer, Richard A %A Lee, C Soon %T p16 and pRb immunohistochemical expression increases with increasing tumour grade in mammary phyllodes tumours. %B Histopathology %D 2010 %C United Kingdom %I Wiley-Blackwell Publishing Ltd. %V 56 %N 7 %P 868-875 %@ 0309-0167 %X Karim R Z, Gerega S K, Yang Y H, Spillane A, Carmalt H, Scolyer R A & Lee C S (2010) Histopathology 56, 868-875 p16 and pRb immunohistochemical expression increases with increasing tumour grade in mammary phyllodes tumours Aims: Control of cell cycling and proliferation is critical to the development of neoplasia and may play a role in the pathogenesis of phyllodes tumours (PTs). This study aimed to evaluate the immunohistochemical expression of certain proteins from the G(1)/S transition of the cell cycle in a cohort of PTs, to determine their role in tumour pathogenesis and to identify any associations with patient outcome. Methods and results: Sixty-five PTs (34 benign, 23 borderline and eight malignant) diagnosed at a single institution between 1990 and 2006 were analysed. Immunohistochemistry for p16, pRb, cyclin D1 and Ki67 was performed. Expression of the following markers increased significantly with tumour grade: stromal nuclear and cytoplasmic p16 (P = 0.01 and 0.002, respectively), stromal and epithelial pRb (P = 0.000 000 06 and 0.004, respectively), and stromal and epithelial Ki67 (P = 0.03 and 0.04, respectively). Epithelial pRb scores of 7 (range 0-7) were significantly associated with reduced disease-free survival (DFS) compared with scores of <7 (P = 0.0009). No relationship was found between cyclin D1 expression in either the epithelium or the stroma, and grade or DFS. Conclusions: The results suggest that alterations at the G(1)/S transition of the cell cycle play an important role in the progression of PTs. %Z FOR Codes: 110316 110323 %0 Journal Article %~ Isi %A Bennett, N. %A Hooper, J. D. %A Lee, C. S. %A Gobe, G. C. %T Androgen Receptor and Caveolin-1 in Prostate Cancer %B Iubmb Life %D 2009 %C United Kingdom %I Wiley-Blackwell Publishing Ltd. %V 61 %N %P 961-970 %@ 1521-6543 %X %Z FOR Codes: 110312 %0 Journal Article %~ PubMed %A Cooper, Wendy A %A Kohonen-Corish, Maija R J %A McCaughan, Brian %A Kennedy, Catherine %A Sutherland, Robert L %A Lee, Cheok Soon %T Expression and prognostic significance of cyclin B1 and cyclin A in non-small cell lung cancer. %B Histopathology %D 2009 %C United Kingdom %I Wiley-Blackwell Publishing Ltd. %V 55 %N 1 %P 28-36 %@ 0309-0167 %X AIMS: Aberrant expression of cell cycle regulators has been implicated in the pathogenesis of many neoplasms, including non-small cell lung cancer (NSCLC). The aim was to examine the expression and prognostic value of cyclin B1 and cyclin A, key regulators of the G(2)/M checkpoint of the cell cycle, in NSCLC and bronchial precursor lesions. METHODS AND RESULTS: Immunohistochemical expression of cyclin B1 and A was examined in 90 cases of stage I-II primary NSCLC and bronchial precursor lesions using tissue microarrays. Increased cyclin B1 and A expression was found in 40.9 and 58.9% of NSCLC cases, respectively, and was significantly higher in primary NSCLC, lymph node metastases and some bronchial precursor lesions compared with normal bronchial epithelium. Increased expression of cyclin A and cyclin B1 correlated with tumour type, poorly differentiated tumours and male gender. A significant association was found between increased cyclin B1 expression and reduced survival using Kaplan-Meier survival analysis. On multivariate analysis, cyclin B1 was not an independent prognostic factor (P = 0.067). Cyclin A expression was not associated with survival. CONCLUSIONS: Cyclin B1 and cyclin A are aberrantly expressed in NSCLC and some precursor lesions. Cyclin B1, but not cyclin A, shows some promise as a potential prognostic marker in NSCLC. %Z FOR Codes: 1004 %0 Journal Article %~ PubMed %A Biankin, Andrew V %A Kench, James G %A Colvin, Emily K %A Segara, Davendra %A Scarlett, Christopher J %A Nguyen, Nam Q %A Chang, David K %A Morey, Adrienne L %A Lee, C-Soon %A Pinese, Mark %A Kuo, Samuel C L %A Susanto, Johana M %A Cosman, Peter H %A Lindeman, Geoffrey J %A Visvader, Jane E %A Nguyen, Tuan V %A Merrett, Neil D %A Warusavitarne, Janindra %A Musgrove, Elizabeth A %A Henshall, Susan M %A Sutherland, Robert L %A , NSW Pancreatic Cancer Network %T Expression of S100A2 Calcium-Binding Protein Predicts Response to Pancreatectomy for Pancreatic Cancer. %B Gastroenterology %D 2009 %C United States %I WB Saunders Co. %V 137 %N 2 %P 558-68, 568.e1-11 %@ 0016-5085 %X Current methods of preoperative staging and predicting outcome following pancreatectomy for pancreatic cancer (PC) are inadequate. We evaluated the utility of multiple biomarkers from distinct biologic pathways as potential predictive markers of response to pancreatectomy and patient survival. %Z FOR Codes: 2201 %0 Journal Article %~ PubMed %A Zhuang, Liquing %A Scolyer, Richard A %A Lee, C Soon %A McCarthy, Stanley W %A Cooper, Wendy A %A Zhang, Xu D %A Thompson, John F %A Hersey, Peter %T Expression of glucose-regulated stress protein GRP78 is related to progression of melanoma. %B Histopathology %D 2009 %C United Kingdom %I Wiley-Blackwell Publishing Ltd. %V 54 %N 4 %P 462-470 %@ 0309-0167 %X AIMS: Glucose-regulated protein 78 (GRP78) is a protein translated in response to endoplasmic reticulum (ER) stress that has been implicated in the pathogenesis and resistance to therapy of a variety of cancers. The aim of this study was to investigate its expression and role in the development and progression of human melanoma. METHODS AND RESULTS: The immunohistochemical expression of GRP78 in naevi, primary melanoma and melanoma metastases from 171 patients was correlated with clinicopathological factors and patient survival. The GRP78 immunoreactivity score (IRS) was 0.2 in compound naevi, 0.65 in dysplastic naevi, 4.65 in naevi adjacent to primary melanoma, 2.4 in melanoma in situ, 11.2 in thin (1.0 mm) primary melanoma. It was 18 and 17.3 in subcutaneous and lymph node metastases, respectively (P < 0.0001). GRP78 expression was positively correlated with increasing tumour thickness (P = 0.001) and with increasing dermal tumour mitotic index (P = 0.0004). Disease-free survival (chi(2) = 8.0703, P = 0.0045) and overall survival (chi(2) = 6.2633, P = 0.0123) in melanoma patients with IRS >25 were significantly lower than in melanoma patients with IRS <25. CONCLUSIONS: GRP78 expression appears to correlate with known correlates of melanoma progression and survival and requires further evaluation as a prognostic biomarker in melanoma. %Z FOR Codes: 1112 %0 Journal Article %~ PubMed %A Wong, M H W %A Dobbins, T A %A Tseung, J %A Tran, N %A Lee, C S %A O'Brien, C J %A Clark, J %A Rose, B R %T Oestrogen receptor beta expression in pleomorphic adenomas of the parotid gland. %B Journal of Clinical Pathology %D 2009 %C United Kingdom %I BMJ Group %V 62 %N 9 %P 789-793 %@ 1472-4146 %X AIMS: Pleomorphic adenomas of the salivary gland have gender and age distributions suggesting that oestrogen has a causal role. However, oestrogen receptor (ER)alpha is expressed at low levels in normal salivary gland tissues and data from salivary gland tumours are conflicting. There is preliminary evidence that the recently described ERbeta may be the major ER in salivary gland tissue. The aim of this study was to determine the nature and extent of ERbeta expression in pleomorphic adenomas of the salivary gland. METHODS: Pleomorphic adenomas and normal tissues of the parotid gland from 49 patients were tested for ERalpha and ERbeta expression by semiquantitative immunohistochemistry. Associations were sought with patient age and gender. RESULTS: ERalpha and ERbeta expression was localised mainly to the nuclei of ductal cells in normal tissues and the epithelial components in pleomorphic adenomas. Within each tissue and receptor type there were no associations between ER positivity and patient age or gender. ERbeta was expressed in almost twice as many normal tissues and pleomorphic adenomas as ERalpha. Expression of ERbeta was also significantly higher in tumour compared with normal tissues. CONCLUSIONS: This is thought to be the first study of ERbeta in pleomorphic adenomas of the salivary gland. Findings support ERbeta as the major ER in salivary glands, and provide evidence that ERbeta may have a role in the development of pleomorphic adenomas of the salivary gland. %Z FOR Codes: 110316 %0 Journal Article %~ PubMed %A Karim, Rooshdiya Z %A Scolyer, Richard A %A Tse, Gary M %A Tan, Puay-Hoon %A Putti, Thomas C %A Lee, C Soon %T Pathogenic mechanisms in the initiation and progression of mammary phyllodes tumours. %B Pathology %D 2009 %C United Kingdom, Australia %I Informa Healthcare %V 41 %N 2 %P 105-117 %@ 0031-3025 %X Mammary phyllodes tumours (PTs) are rare fibroepithelial neoplasms of the breast. They have a propensity to recur locally and the ability to metastasise. There is some correlation between the histological parameters of PTs and their biological behaviour; however, no single feature or grading scheme can accurately predict the behaviour of a PT. The PTs that will recur and/or metastasise are not being precisely delineated with the currently available diagnostic tools. A number of pathways/markers have been implicated in the pathogenesis of PTs including hormone receptors, members of the Wnt pathway, cell cycle proteins, factors involved in angiogenesis, tyrosine kinase receptors and matrix metalloproteases. The currently available evidence supports a model where initiation of PTs involves interactions between the epithelium and stroma and these interactions are lost with the progression to malignancy such that growth of the stroma becomes autonomous of the epithelium. Loss of the stromal-epithelial interdependancy, increased stromal proliferation, angiogenesis and matrix alterations appear to be involved in the progression to malignancy. %Z FOR Codes: 110316 %0 Journal Article %~ PubMed %A Karim, R Z %A Gerega, S K %A Yang, Y H %A Spillane, A %A Carmalt, H %A Scolyer, R A %A Lee, C S %T Phyllodes tumours of the breast: a clinicopathological analysis of 65 cases from a single institution. %B Breast %D 2009 %C United Kingdom %I Churchill Livingstone %V 18 %N 3 %P 165-170 %@ 0960-9776 %X The aim of this study was to document the clinical and pathological features of a large single institutional series of ethnically diverse patients with phyllodes tumours (PTs), and to determine which characteristics were predictive of outcome. Sixty five PTs were analysed; 34 were benign, 23 borderline and eight malignant (34 low grade and 31 high grade PTs on a two tiered grading system). Nine patients (15%) had local recurrences. A greater percentage of higher grade tumours recurred and women of Asian origin had a higher recurrence rate compared to the non-Asian patients. The 5 year disease-free survival was 81% and time to recurrence was significantly lower in the high grade group. No metastases or deaths from disease were recorded. The mean age at diagnosis significantly increased with tumour grade. The mean tumour volume also significantly increased with grade. Tumour grade was the only parameter related significantly to outcome. %Z FOR Codes: 111209 %0 Journal Article %~ PubMed %A Fei, Jimin %A Hong, Angela %A Dobbins, Timothy %A Jones, Deanna %A Soon Lee, C %A Loo, Christine %A Al-Ghamdi, Mohammad %A Harnett, Gerald %A Clark, Jonathan %A O'Brien, Christopher %A Rose, Barbara %T Prognostic Significance of Vascular Endothelial Growth Factor in Squamous Cell Carcinomas of the Tonsil in Relation to Human Papillomavirus Status and Epidermal Growth Factor Receptor. %B Annals of surgical oncology %D 2009 %C United States %I Springer New York LLC %V 16 %N 10 %P 2908-17 %@ 1068-9265 %X Angiogenesis markers, vascular endothelial growth factor (VEGF) and microvessel density (MVD) have been associated with prognosis in squamous cell carcinomas (SCCs) of the head and neck. Other prognostic variables such as human papillomavirus (HPV) and epidermal growth factor (EGFR) may also be involved in tumour angiogenesis. This study determined relationships between VEGF, MVD, EGFR, HPV, response to radiotherapy and clinical outcome in 85 tonsillar SCCs. %Z FOR Codes: 111202 110309 %0 Journal Article %~ PubMed %A Karim, R Z %A Gerega, S K %A Yang, Y H %A Horvath, L %A Spillane, A %A Carmalt, H %A Scolyer, R A %A Lee, C S %T Proteins from the Wnt pathway are involved in the pathogenesis and progression of mammary phyllodes tumours. %B Journal of Clinical Pathology %D 2009 %C United Kingdom %I BMJ Group %V 62 %N 11 %P 1016-1020 %@ 1472-4146 %X BACKGROUND: The Wnt pathway is important in cell signalling transduction and is involved in the pathogenesis of multiple tumour types. A comprehensive analysis of the expression of Wnt signalling pathway proteins in mammary phyllodes tumours (PTs) has not been previously performed. AIMS: To evaluate the immunohistochemical expression of Wnt pathway proteins in a cohort of PTs, to determine their role in tumour pathogenesis and to identify any associations with patient outcome. METHODS: 65 PTs (34 benign, 23 borderline and 8 malignant) diagnosed at a single institution between 1990 and 2006 were analysed. Immunohistochemical stains were performed on tissue microarrays for beta-catenin, Wnt1, Wnt5a, SFRP4 and E-cadherin. Stroma and epithelium were scored separately. RESULTS: Stromal cytoplasmic Wnt5a and SFRP4 expression showed significant progressive increases in expression with increasing grade (p = 0.002 and p = 0.02 respectively). Epithelial membranous and stromal nuclear beta-catenin, epithelial cytoplasmic Wnt1 and epithelial E-cadherin all also showed increasing expression with increasing tumour grade, however, the differences were not significant. Disease-free survival was significantly decreased (p = 0.0017) with positive epithelial E-cadherin staining. CONCLUSIONS: Results suggest that alterations in the Wnt pathway are important in the progression and in the epithelial and stromal interactions in PTs. They have important implications for understanding the pathogenesis of these uncommon but clinically important tumours. %Z FOR Codes: 110399 %0 Journal Article %~ PubMed %A Yu, Denise M T %A Ajami, Katerina %A Gall, Margaret G %A Park, Joohong %A Lee, C Soon %A Evans, Kathryn A %A McLaughlin, Eileen A %A Pitman, Melissa R %A Abbott, Catherine A %A McCaughan, Geoffrey W %A Gorrell, Mark D %T The In Vivo Expression of Dipeptidyl Peptidases 8 and 9. %B The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society %D 2009 %C United States %I Histochemical Society %V 57 %N 11 %P 1025-40 %@ 0022-1554 %X The dipeptidyl peptidase IV (DPIV) enzyme family contains both potential and proven therapeutic targets. Recent reports indicate the presence of DP8 and DP9 in peripheral blood lymphocytes, testis, lung, and brain. For a more comprehensive understanding of DP8 and DP9 tissue and cellular expression, mRNA and enzyme activity were examined. Many organs from C57BL/6 wild-type and DPIV gene-knockout mice were examined; DP8/9 enzyme activity was detected in the immune system, brain, testis, muscle, and epithelia. In situ hybridization localized DP8 and DP9 mRNA to lymphocytes and epithelial cells in liver, gastrointestinal tract, lymph node, spleen, and lung. DP8 and DP9 mRNA was detected in baboon and mouse testis, and DP9 expression was elevated in human testicular cancers. DP8 and DP9 mRNA were ubiquitous in day 17 mouse embryo, with greatest expression in epithelium (skin and gastrointestinal tract) and brain. Thus, DP8 and DP9 are widely expressed enzymes. Their expression in lymphocytes and epithelia indicates potential for roles in the digestive and immune systems. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials. %Z FOR Codes: 110307 110704 110306 %0 Journal Article %~ PubMed %A Seng, T J %A Currey, N %A Cooper, W A %A Lee, C-S %A Chan, C %A Horvath, L %A Sutherland, R L %A Kennedy, C %A McCaughan, B %A Kohonen-Corish, M R J %T DLEC1 and MLH1 promoter methylation are associated with poor prognosis in non-small cell lung carcinoma. %B British journal of cancer %D 2008 %C United Kingdom %I Nature Publishing Group %V 99 %N 2 %P 375-82 %@ 1532-1827 %X The significance of chromosome 3p gene alterations in lung cancer is poorly understood. This study set out to investigate promoter methylation in the deleted in lung and oesophageal cancer 1 (DLEC1), MLH1 and other 3p genes in 239 non-small cell lung carcinomas (NSCLC). DLEC1 was methylated in 38.7%, MLH1 in 35.7%, RARbeta in 51.7%, RASSF1A in 32.4% and BLU in 35.3% of tumours. Any two of the gene alterations were associated with each other except RARbeta. DLEC1 methylation was an independent marker of poor survival in the whole cohort (P=0.025) and in squamous cell carcinoma (P=0.041). MLH1 methylation was also prognostic, particularly in large cell cancer (P=0.006). Concordant methylation of DLEC1/MLH1 was the strongest independent indicator of poor prognosis in the whole cohort (P=0.009). However, microsatellite instability and loss of MLH1 expression was rare, suggesting that MLH1 promoter methylation does not usually lead to gene silencing in lung cancer. This is the first study describing the prognostic value of DLEC1 and MLH1 methylation in NSCLC. The concordant methylation is possibly a consequence of a long-range epigenetic effect in this region of chromosome 3p, which has recently been described in other cancers. %Z FOR Codes: 111202 %0 Journal Article %~ PubMed %A Lee, C Soon %T Editorial: Pathology in its fortieth year. %B Pathology %D 2008 %C United Kingdom %I Carfax Publishing %V 40 %N 1 %P 1-2 %@ 0031-3025 %X %Z FOR Codes: 110316 %0 Journal Article %~ PubMed %A Murphy, N C %A Scarlett, C J %A Kench, J G %A Sum, E Y M %A Segara, D %A Colvin, E K %A Susanto, J %A Cosman, P H %A Lee, C-S %A Musgrove, E A %A Sutherland, R L %A Lindeman, G J %A Henshall, S M %A Visvader, J E %A Biankin, A V %T Expression of LMO4 and outcome in pancreatic ductal adenocarcinoma. %B British journal of cancer %D 2008 %C United Kingdom %I Nature Publishing Group %V 98 %N 3 %P 537-541 %@ 1532-1827 %X Identification of a biomarker of prognosis and response to therapy that can be assessed preoperatively would significantly improve overall outcomes for patients with pancreatic cancer. In this study, patients whose tumours exhibited high LMO4 expression had a significant survival advantage following operative resection, whereas the survival of those patients whose tumours had low or no LMO4 expression was not significantly different when resection was compared with operative biopsy alone. %Z FOR Codes: 111201 %0 Journal Article %~ PubMed %A Tse, Gary %A Lui, Philip %A Vong, Joaquim %A Lau, Kin-Mang %A Putti, Thomas %A Karim, Rooshdiya %A Scolyer, Richard %A Lee, C-Soon %A Yu, Alex %A Ng, David %A Tse, Agnes %A Tan, Puay-Hoon %T Increased epidermal growth factor receptor (EGFR) expression in malignant mammary phyllodes tumors. %B Breast cancer research and treatment %D 2008 %C US %I Kluwer Academic Publishers %V 114 %N 0 %P 441-8 %@ 0167-6806 %X Mammary phyllodes tumors are uncommon stromal-epithelial neoplasms, and are divided into benign, borderline malignant and frankly malignant groups on the basis of their histological features. Accumulating evidence shows that epidermal growth factor receptor (EGFR) is involved in the pathogenesis and progression of many malignancies. This study investigated 453 phyllodes tumors (296 benign, 98 borderline, 59 malignant) for EGFR expression using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) for gene amplification. The staining was correlated to tumor margin status, degree of malignancy, stromal cellularity, mitotic activity, nuclear pleomorphism and stromal overgrowth. Cases with strong positive IHC staining were selected for FISH. The overall positive rate for EGFR was 16.2% (48/296), 30.6% (30/98) and 56% (33/59) for benign, borderline malignant and frankly malignant phyllodes tumors, respectively. FISH demonstrated egfr gene amplification in 8% of immunohistochemically positive cases. The results of this study provide strong evidence that EGFR overexpression is involved in the pathogenesis of phyllodes tumors, although gene amplification may not be the major underlying mechanism for overexpression. %Z FOR Codes: 111299 %0 Journal Article %~ PubMed %A Cooper, W A %A Kohonen-Corish, M R J %A Chan, C %A Kwun, S Y %A McCaughan, B %A Kennedy, C %A Sutherland, R L %A Lee, C-S %T Prognostic significance of DNA repair proteins MLH1, MSH2 and MGMT expression in non-small-cell lung cancer and precursor lesions. %B Histopathology %D 2008 %C United Kingdom %I Blackwell Publishing Ltd %V 52 %N 5 %P 613-622 %@ 0309-0167 %X AIMS: To investigate the role of DNA repair proteins and their prognostic significance in non-small-cell lung cancer (NSCLC). METHODS AND RESULTS: A retrospective analysis of 108 cases of stage I-II NSCLC was undertaken. Immunohistochemical expression of DNA repair proteins MLH1, MSH2 and MGMT was assessed using tissue microarrays of paraffin-embedded samples of invasive carcinoma and precursor lesions. Results were analysed in relation to clinicopathological parameters and patient survival. Reduced expression of MLH1 was found in 58.5% of tumours and occurred less frequently in poorly differentiated tumours (P = 0.044) and large cell carcinomas (P = 0.004). MSH2 and MGMT expression was reduced in 18.1% and 77.8% of cases, respectively. There was an inverse relationship between MLH1 and MSH2 expression (P = 0.012). Normal expression of MLH1, MSH2 and MGMT was found in all cases of squamous metaplasia and squamous dysplasia. Only a single case of carcinoma in situ (12.5%) showed reduced MLH1, none showed reduced MSH2 and 25% showed reduced MGMT. Survival analyses showed no prognostic significance based on expression of MLH1 (P = 0.92), MSH2 (P = 0.78) or MGMT (P = 0.57). CONCLUSIONS: Reduction in expression of DNA repair proteins MLH1, MSH2 and MGMT is relatively common in NSCLC, appears to be a late event in the development of invasive malignancy and does not influence survival in this patient cohort. %Z FOR Codes: 110323 111203 %0 Journal Article %~ PubMed %A Cooper, Wendy A %A Kohonen-Corish, Maija R J %A Zhuang, Liqing %A McCaughan, Brian %A Kennedy, Catherine %A Screaton, Gavin %A Sutherland, Robert L %A Lee, C-Soon %T Role and prognostic significance of tumor necrosis factor-related apoptosis-inducing ligand death receptor DR5 in nonsmall-cell lung cancer and precursor lesions. %B Cancer %D 2008 %C United States %I John Wiley & Sons Inc %V 113 %N 1 %P 135-42 %@ 0008-543X %X The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) death receptor, DR5, mediates proapoptotic signals and is implicated in the pathogenesis of many neoplasms including nonsmall-cell lung cancer (NSCLC). %Z FOR Codes: 110323 111201 %0 Journal Article %~ PubMed %A Patel, R S %A Hughes, C W %A Fredericks, S %A Lee, C S %A Rose, B %A Gao, K %A Smith, G %A Hong, A %A O'brien, C J %T Cyclin A expression and its diagnostic value in pleomorphic adenoma and carcinoma expleomorphic adenoma of the parotid gland. %B Histopathology %D 2007 %C United Kingdom %I Blackwell Publishing Ltd. %V 51 %N 1 %P 21-25 %@ 0309-0167 %X Aims: To investigate cyclin A expression in pleomorphic adenoma (PA) and carcinoma expleomorphic adenoma (CXPA) of the parotid gland with a view to assessing its potential value as a diagnostic marker for CXPA. Methods and results: Cyclin A expression in PA and CXPA was studied using semiquantitiative immunohistochemistry. The epithelial component of the tumours expressed cyclin A in a statistically significantly (P < 0.005) higher number of CXPA cases (86%) compared with the PA cases (39%). Cyclin A was not expressed in normal salivary tissues of PA and CXPA. Conclusions: High cyclin A expression is a useful marker for the pathological diagnosis of CXPA. %Z FOR Codes: 110316 %0 Journal Article %~ PubMed %A Patel, R S %A Rose, B %A Bawdon, H %A Hong, A %A Lee, C S %A Fredericks, S %A Gao, K %A O'brien, C J %T Cyclin D1 and p16 expression in pleomorphic adenoma and carcinoma ex pleomorphic adenoma of the parotid gland. %B Histopathology %D 2007 %C United Kingdom. %I Wiley- Blackwell Publishing Ltd. %V 51 %N 5 %P 691-696 %@ 0309-0167 %X Aims: To compare cyclin D1 and p16(ink4) (p16) expression in normal tissue, pleomorphic adenoma (PA) and carcinoma ex pleomorphic adenoma (CXPA) of the parotid gland. Methods and results: Immunohistochemistry was used to examine cyclin D1 and p16 expression in 43 parotid tumours (29 PAs and 14 CXPAs). Cyclin D1 and p16 were both significantly more likely to be expressed in the neoplastic than in the normal epithelial and stromal components of PA and CXPA (P < 0.001 and P < 0.005, respectively). Cyclin D1 was more likely to be expressed in the malignant components of CXPA than in the benign components of PA (50% versus 31% and 31%, respectively), but the trend was not statistically significant. There was no evidence of this association for p16 (corresponding positivity rates 69% versus 81% and 52%). Conclusions: Our findings provide preliminary evidence of roles for cyclin D1 and p16 in the development of PA and for cyclin D1 in the progression of PA to CXPA. %Z FOR Codes: 110323 111201 %0 Journal Article %~ PubMed %A Murali, Rajmohan %A Doubrovsky, Anna %A Watson, Geoffrey F %A McKenzie, Paul R %A Lee, C Soon %A McLeod, Duncan J %A Uren, Roger F %A Stretch, Jonathan R %A Saw, Robyn P M %A Thompson, John F %A Scolyer, Richard A %T Diagnosis of metastatic melanoma by fine-needle biopsy: analysis of 2,204 cases. %B American journal of clinical pathology %D 2007 %C United States %I American Society for Clinical Pathology %V 127 %N 3 %P 385-397 %@ 0002-9173 %X Fine-needle biopsy (FNB) has been reported as a rapid, minimally invasive technique for the diagnosis of metastatic melanoma. The diagnostic accuracy of FNB was assessed in a consecutive series of 2,204 FNBs of clinically suspicious lesions from patients with previous primary melanomas treated at the Sydney Melanoma Unit, Sydney, Australia, between January 1992 and December 2002. The sensitivity and specificity of FNB were 96.3% and 98.9%, respectively. There were 5 false-positive cases (0.6%), which were verified as metastatic adenocarcinoma (3 cases) or reactive processes (organizing hematoma and chronic osteomyelitis, 1 each). False-negative diagnoses (6.7% of cases) were associated with a variety of clinicopathologic factors, including difficult-to-access anatomic sites (eg, high axilla or deep inguinal), small lesions, and lesional characteristics such asfibrosis, necrosis, or cystic change. FNB is a highly accurate, rapid, and cost-effective procedure for the diagnosis of metastatic melanoma and should be considered as the initial diagnostic procedure of choice in patients with melanoma with clinically suspected metastases. %Z FOR Codes: 110316 %0 Journal Article %~ PubMed %A Doubrovsky, Anna %A Scolyer, Richard %A Murali, Rajmohan %A McKenzie, Paul %A Watson, Geoffrey %A Lee, C %A McLeod, Duncan %A McCarthy, William %A Uren, Roger %A Stretch, Jonathan %A Saw, Robyn %A Thompson, John %T Diagnostic Accuracy of Fine Needle Biopsy for Metastatic Melanoma and Its Implications for Patient Management. %B Annals of surgical oncology %D 2007 %C US %I Springer-Verlag New York, Inc. %V 15 %N 0 %P 323-32 %@ 1068-9265 %X The use of fine needle biopsy (FNB) for the diagnosis of metastatic melanoma can lead to the early removal and treatment of metastases, reduce the frequency of unnecessary surgery, and facilitate the staging of patients enrolled in clinical trials of adjuvant therapies. In this study, the accuracy of FNB for the diagnosis of metastatic melanoma was investigated. %Z FOR Codes: 110316 111201 %0 Journal Article %~ PubMed %A Tse, Gary M %A Chaiwun, Benjaporn %A Lau, Kin-Mang %A Scolyer, Richard %A Lee, C Soon %A Karim, Rooshdiya Z %A Putti, Thomas C %A Law, Bonita K %A Lui, Philip C %A Tan, Puay Hoon %T Endothelin-1 expression correlates with atypical histological features in mammary phyllodes tumours. %B Journal of clinical pathology %D 2007 %C United Kingdom %I British Med Journal Publ Group %V 60 %N 9 %P 1051-1056 %@ 0021-9746 %X Background and AIMS: Endothelin-1 expression is increased in infiltrating duct carcinoma and is associated with larger tumour size, higher histological grade and lymphovascular permeation. This has not been evaluated in phyllodes tumours, which are uncommon fibroepithelial lesions with potential for local recurrences or distant metastasis. While the grading of phyllodes tumours depends on a combination of histological parameters, prediction of their behaviour remains difficult. Method: A large series of 461 phyllodes tumours (291 benign, 115 borderline malignant and 55 frankly malignant) were evaluated for endothelin-1 expression in both the epithelial cells and stromal cells by immunohistochemistry; results were correlated with the tumour grade. RESULTS: For benign phyllodes tumours, the epithelial staining of endothelin was negative, weak, moderate and strong in 6%, 26%, 15% and 53% of cases respectively; results were 4%, 18%, 19% and 59% respectively for borderline and 6%, 18%, 6% and 70% respectively for frankly malignant tumours. For the stromal staining, the negative, weak, moderate and strong staining was 32%, 19%, 18% and 31% respectively for benign phyllodes, 24%, 13%, 10% and 53% respectively for borderline and 8%, 16%, 17% and 59% respectively for frankly malignant tumours. There was correlation between epithelial and stromal staining, and the stromal staining correlated with histological features of stromal cellularity, stromal cell nuclear pleomorphism, margin status and stromal overgrowth. CONCLUSION: These observations suggest a close relationship between the epithelial and stromal elements in phyllodes tumours; endothelin may play a significant role in the malignant progression of phyllodes tumours. %Z FOR Codes: 110316 111201 %0 Journal Article %~ PubMed %A Cooper, C L %A Joshua, D E %A Lee, C S %A Eyers, A A %A Cooper, W A %T Extranodal plasmablastic lymphoma arising in mantle cell lymphoma. %B Histopathology %D 2007 %C United Kingdom %I Wiley-Blackwell Publishing Ltd. %V 51 %N 6 %P 856-9 %@ 0309-0167 %X %Z FOR Codes: %0 Journal Article %~ PubMed %A Zhuang, Liqing %A Lee, C Soon %A Scolyer, Richard A %A McCarthy, Stanley W %A Zhang, Xu Dong %A Thompson, John F %A Hersey, Peter %T Mcl-1, Bcl-XL and Stat3 expression are associated with progression of melanoma whereas Bcl-2, AP-2 and MITF levels decrease during progression of melanoma. %B Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc %D 2007 %C United Kingdom %I Nature Publishing Group %V 20 %N 4 %P 416-426 %@ 0893-3952 %X Members of the Bcl-2 family of antiapoptotic proteins (Bcl-2, Bcl-XL and Mcl-1) are key regulators of apoptosis. The purpose of the present study was to examine and better define the role of Bcl-2, Bcl-XL and Mcl-1 in the progression of melanoma. Immunohistochemical staining for Bcl-2, Bcl-XL and Mcl-1 was performed on paraffin sections of 100 cases of benign nevi, primary melanoma and metastatic melanoma. Expression was correlated with histopathologic features, clinical progress and expression of transcription factors (AP-2, MITF and p-Stat3). Bcl-2 was expressed in 100% of benign nevi and thin melanoma (1.0 mm) (88%), subcutaneous (62%) and lymph node metastases (35%). In contrast, Bcl-XL and Mcl-1 were expressed at lower levels in nevi and thin melanoma compared to Bcl-2 but their expression was much higher in thick melanoma and in subcutaneous and lymph node metastases (P<0.0001). Bcl-2 expression was negatively associated with tumor thickness (P<0.05) but Bcl-XL expression increased with increasing tumor thickness (P<0.05) and dermal tumor mitotic rate (P<0.05). Similarly Mcl-1 expression increased with increasing tumor thickness (P<0.09) and dermal tumor mitotic rate (P<0.17). Bcl-2 expression was positively correlated with expression of the transcription factors microphthalmia transcription factor (MITF) and nuclear AP-2 whereas Bcl-XL (and Mcl-1) expression were positively correlated with p-Stat3. This study is the first to show a clear dissociation between changes in Bcl-2 expression (downregulation) and Bcl-XL, Mcl-1 expression (upregulation) during progression of melanoma. The results were also consistent with a role for AP-2 and MITF in regulation of Bcl-2 and pStat3 in regulation of Bcl-XL. These findings have important implications for the development of treatments targeting antiapoptotic proteins in patients with melanoma. %Z FOR Codes: 110316 %0 Journal Article %~ PubMed %A Kaufman, Antony %A Storey, David %A Lee, Cheok Soon %A Murali, Rajmohan %T Mucinous cyst exhibiting severe dysplasia in gastric heterotopic pancreas associated withe gastrointestinal stromal tumour. %B World journal of gastroenterology : WJG %D 2007 %C China %I WJD Press %V 13 %N 43 %P 5781-5782 %@ 1007-9327 %X Heterotopic pancreatic tissue within the stomach is rare and dysplasia within heterotopic pancreatic tissue is very rare. We present the first report of a patient with concurrent occurrence of heterotopic pancreas in the stomach with a gastrointestinal stromal tumour. %Z FOR Codes: 110316 %0 Journal Article %~ PubMed %A Horvath, Lisa G %A Lelliott, Jayne E %A Kench, James G %A Lee, C-Soon %A Williams, Elizabeth D %A Saunders, Darren N %A Grygiel, John J %A Sutherland, Robert L %A Henshall, Susan M %T Secreted frizzled-related protein 4 inhibits proliferation and metastatic potential in prostate cancer. %B The Prostate %D 2007 %C United States %I John Wiley & Sons, Inc %V 67 %N 10 %P 1081-1090 %@ 0270-4137 %X BACKGROUND: Secreted frizzled-related proteins (sFRP4) inhibits Wnt signaling and thus cellular proliferation in androgen-independent prostate cancer cells in vitro. However, increased expression of membranous sFRP4 is associated with a good prognosis in human localized androgen-dependent prostate cancer, suggesting a role for sFRP4 in early stage disease. Here, we investigated the phenotype of sFRP4 overexpression in an androgen-dependent prostate cancer model. METHODS: An sFRP4-overexpressing androgen-dependent (LNCaP) prostate cancer model was established to assess changes in cellular proliferation, the expression, and subcellular localization of adhesion molecules and cellular invasiveness, and compared with the findings in sFRP4-overexpressing androgen-independent cells (PC3). RESULTS: sFRP4 overexpression in both cell line models resulted in a morphologic change to a more epithelioid cell type with increased localization of beta-catenin and cadherins (E-cadherin in LNCaP, N-cadherin in PC3) to the cell membrane. Functionally, sFRP4 overexpression was associated with a decreased rate of proliferation (P = 0.0005), decreased anchorage-independent growth (P < 0.001), and decreased invasiveness in PC3 cells (P < 0.0001). Furthermore, increased membranous sFRP4 expression was associated with increased membranous beta-catenin expression (P = 0.02) in a cohort of 224 localized human androgen-dependent prostate cancers. CONCLUSIONS: These data suggest that sFRP4 is an inhibitor of prostate cancer growth and invasion in vitro independent of androgen receptor (AR) signaling with correlative evidence in human androgen-dependent disease suggesting similar changes in the clinical setting. Consequently, potential therapeutic strategies to modulate Wnt signaling by sFRP4 will be relevant to both localized androgen-dependent prostate cancer and advanced metastatic disease. %Z FOR Codes: 111201 110306 %0 Journal Article %~ PubMed %A Murali, Rajmohan %A Sharma, Raghwa %A Thompson, John %A Stretch, Jonathan %A Lee, C %A McCarthy, Stanley %A Scolyer, Richard %T Sentinel Lymph Node Biopsy in Histologically Ambiguous Melanocytic Tumors With Spitzoid Features (So-Called Atypical Spitzoid Tumors). %B Annals of surgical oncology %D 2007 %C US %I Springer-Verlag New York, Inc. %V 15 %N 0 %P 302-9 %@ 1068-9265 %X The distinction of Spitz nevi from melanomas with spitzoid morphology can be difficult. For lesions with overlapping histopathologic features, it may be impossible to predict their malignant potential with certainty. The current study evaluated the role of sentinel lymph node (SLN) biopsy in patients with such atypical spitzoid tumors. %Z FOR Codes: 110316 111201