Trop-2 overexpression as an independent marker for poor overall survival in ovarian carcinoma patients

Background: Prognostic factors currently available are insufficient to predict the clinical course of epithelial ovarian cancer (EOC). In a previous microarray study we identified the human trophoblast cell surface antigen Trop-2 as one of the top differentially expressed genes in serous papillary EOCs compared to normal human ovarian surface epithelial (HOSE) short-term cultures. The aim of the present investigation was to analyse Trop-2 expression at mRNA and protein level and to assess its prognostic significance in EOC. Methods: Using quantitative real-time PCR we tested a total of 104 fresh-frozen EOC tissues and 24 HOSE for Trop-2 mRNA expression. Trop-2 protein expression was then examined by immunohistochemistry in matched formalin-fixed paraffin-embedded EOC samples and in 13 normal ovaries. Finally, we correlated Trop-2 expression to EOC conventional clinicopathological features and patient outcomes. Results: We found a significant Trop-2 mRNA and protein upregulation in EOCs compared to normal controls (p <0.001). Trop-2 protein overexpression was significantly associated with the presence of ascites (p =0.04) and lymph node metastases (p =0.04). By univariate survival analysis, Trop-2 protein overexpression was significantly associated with decreased progression-free (p =0.02) and overall survival (p =0.01). Importantly, Trop-2 protein overexpression was an independent prognostic marker for shortened survival time in multivariate Cox regression analysis (p =0.04, HR=2.35, CI95% =1.03–5.34). Conclusions: Our results indicate, for the first time, that Trop-2 protein overexpression correlates with an aggressive malignant phenotype and may constitute a novel prognostic factor for EOC. The targeting of Trop-2 overexpression by immunotherapeutic strategies may represent an attractive and potentially effective approach in patients harbouring EOC. [Copyright &y& Elsevier]