Thesis abstract:

Improving the Diagnosis and Treatment of Carcinoma of Unknown Primary Using Proteomics

Carcinoma of unknown primary (CUP) is a term used to describe a heterogenous group of cancers in which the primary site of disease cannot be identified. Patients with CUP have a poor prognosis and new approaches to diagnosis are urgently needed to be able to more effectively treat these cancers (1, 2). Given it is largely accepted that CUP patients have a primary site that is simply not detectable by conventional means, various methods have been employed to improve diagnosis and subsequently guide treatment. The gold standard pathological assessment, immunohistochemistry (IHC), has several limitations including poor reproducibility, sensitivity, specificity as well as time delay in achieving a diagnosis of CUP given sequential rounds of complicated IHC assessment are required to exclude cancer subtypes (3). Molecular tissue of origin-based testing has been proposed as an alternative means to diagnosis, however, this has not widely replaced IHC due to a lack of prospective data showing improvement in outcomes, availability and cost considerations (4).Clinical proteomics is an evolving field which has the potential to improve the accuracy of diagnosis and increase the depth of understanding of CUP biology (5). This project will focus on developing and validating a diagnostic profile for CUP to improve diagnosis and inform treatment for this challenging group of patients.