Construction of a Tissue Microarray for Validation of EphA2 Receptor as a Prostate Cancer Biomarker

Abstract

Introduction: Prostate cancer is the most common non-cutaneous male cancer, with an increasing incidence secondary to PSA use. There remains much uncertainty regarding its natural history, and thus further uncertainty surrounding treatment with subsequent under- and over-treatment. There is an association with diet, particularly diets high in Ω6 polyunsaturated fatty acids such as arachidonic acid. Arachidonic acid may promote the metastasis-like behaviour of epithelial to mesenchymal transition of prostate cancer cells via the EphA2 pathway. In an initial study, EphA2 expression was shown to correlate in prostate cancer specimens to overall survival suggesting use as a biomarker. The aim of this project was to construct a new tissue microarray for validation of EphA2 as a biomarker. Methods: Electronic patient records were reviewed to update the Salford Royal Prostate Cancer database. Samples were identified from the Salford Royal Prostate Cancer tissue bank. H&E slides were reviewed to identify areas of prostate cancer to be isolated for construction of a new tissue microarray. An immunofluorescence protocol using the Ventana system was optimised to assess EphA2 expression. Results: A total of 296 patients were included within the new tissue microarray. Sample size calculations showed that this is of a sufficient size to validate earlier findings regarding overall survival, metastatic disease, and biochemical progression, but not prostate cancer death. The validation cohort was comparable both with the original tissue microarray cohort in terms of age, stage, Gleason score, biochemical progression, and overall survival. Results were also comparable to national data. Discussion: EphA2 has shown potential to be a prostate cancer biomarker to predict for overall survival, metastasis, and biochemical progression. This project has resulted in the construction of a sufficiently sized new tissue microarray from patients with prostate cancer TRUS biopsies at the time of diagnosis with an extensive follow-up. This may potentially be used to validate initial findings but also act as a resource for assessment of future prostate cancer biomarkers.

Date of Award	1 Aug 2020
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Michael Brown (Supervisor) & Noel Clarke (Supervisor)