EXPRESSION OF ERG AND SPINK1 IN PROSTATE CARCINOMA AND ITS CORRELATION WITH CLINICO PATHOLOGICAL PARAMET

Abstract

Prostate cancer is the second most common adult male malignancy worldwide and rank 6 th in Pakistan. Altered genes play a driving role in cancer development and can serve as specific diagnostic and prognostic biomarkers. TMPRSS2:ERG fusion is the commonest molecular alteration present in more than 50% of prostate cancers this leads to overexpression of ERG which can be observed on immunohistochemistry. The serine peptidase inhibitor kazal type1 (SPINK1) is suggested to be an aggressive molecular subtype of ERG fusion negative Prostate cancer and is associated with poor prognosis. The aim of this study was to evaluate the expression of ERG and SPINK1 in prostate cancer and BPH samples and to determine their co-relation with various clinic pathological parameters. A cross-sectional study was conducted in PNS Shifa Hospital, Karachi, over a period of one year. 33 cases of prostate cancer and 7 cases of BPH were retrieved and examined for immunohistochemical expression of ERG and SPINK1. The results of immunohistochemistry were correlated with various clinicopathological parameters namely age, clinical presentation, Gleason score, Gleason grade group, lymphovascular invasion, perineural invasion and intraductal carcinoma. Out of 33 cases of prostate carcinoma 20 (60.6%) showed ERG expression and none of BPH sample expressed ERG. Among 13 ERG negative prostate carcinoma cases SPINK1 expression was observed in only three cases, thus undermining its significance as a diagnostic marker or a marker of advance lesions. ERG expression was seen in both high and low grade prostate carcinoma, suggesting TMPRSS2-ERG fusion as an early event in carcinogenesis of these tumors and its persistence throughout the disease. One case expressed both ERG and SPINK1 thus questioning the mutual exclusivity of the expression of these markers. The current study is expected to pave way for further researches regarding the effectiveness of these two markers as diagnostic/prognostic markers and as therapeutic targets for prostate carcinomas.