IMMUNOHISTOCHEMICAL EVALUATION OF PARP AND CASPASE-3 AS PROGNOSTIC MARKERS IN PROSTATE CARCINOMAS

Prostate cancer (PCa) is the second most commonly occurring cancer in men. As a heterogeneous disease with variable outcomes, treatment options for advanced stages remain challenging. Research in mechanisms involved in cell death resistance and apoptosis evasion is of high importance for the study of biomarkers which may not only predict disease progression, but also guide therapeutic strategies. Poly (ADP-ribose) polymerase (PARP) are a family of enzymes responsible for the maintenance of genomic integrity, acting in DNA damage repair, and might be related to tumor cells survival and resistance to antineoplastic therapy. Caspase-3 is an abundant protein in apoptotic cells, taking important part in cell death events. The aim of the present study was to evaluate PARP and caspase-3 expression in PCa samples in a retrospective study, investigating the relation between this anti and pro-apoptotic proteins and patients prognosis. Tumor fragments were selected from 29 patients and protein expression was analyzed by immunohistochemistry. Patients were previously classified as good prognosis (n=16) and poor prognosis (n=13), being the criteria fundamentally based on each patient☐s clinical evolution, as this is a retrospective study. Immunohistochemical assay was performed for both proteins and all reactions were followed by a positive and negative control for each tested antibody. Analysis of the expression quantified by optical densitometry revealed significantly elevated level of PARP expression in tumors from patients with poor prognosis, when compared to its expression in the good prognosis group (P<0,0001). Patients previously classified as poor prognosis revealed lower levels of caspase-3 expression, when compared with the good prognosis group, which showed higher levels of caspase-3 (p=0,0007). The groups were stratified according to six clinicopathological parameters. Simultaneous influence of this factors and patient’s prognosis was analyzed, being statistically correlated to higher PARP expression and age at diagnosis over 70(p=0,0001) and also to belonging to unfavorable risk group (p=0,033). Our results suggest a potential role for PARP and caspase-3 as prognostic markers in PCa. The combined analysis of both proteins with antagonistic functions in this context of disease progression and disclosure may provide predictive data on the behavior of prostate cancer and patient’s clinical outcome.