Avaliação imuno-histoquímica de PARP1 e CASPASE-3 como marcadores prognósticos em carcinomas de próstata

Abstract

Prostate cancer (PC) is a neoplasm with a high global incidence and variable behavior, the evolution of which can cause serious and lethal complications. Due to the heterogeneous nature of the disease, therapeutic approaches vary according to the presentation of the initial condition, therefore, it is increasingly important to find predictive biomarkers in order to improve the prognosis and treatment of the disease. The study of the mechanisms involved in tumor resistance and avoidance of apoptosis is fundamental for the discovery of biomarkers that help to predict its progression and guide therapeutic decisions. The family of PARP enzymes (poly ADP-ribose polymerase) maintains genomic integrity and detects DNA damage acting on repair, which may be related to the survival of the tumor cell and resistance to antineoplastic therapy. CASPASE-3 is a protein present in apoptotic cells that participates in the events of cell death. Objective: To investigate in a retrospective study the relationship between the immunohistochemical expression of proteins PARP1 AND CASPASE-3, with the clinical features and prognosis of patients with prostate cancer. Materials and Methods: Paraffin blocks of 29 men treated and diagnosed with prostate cancer were selected at the Oncology Sector of the Medical School of São José do Rio Preto - FAMERP in the period from 2011 to 2012. All information on the clinical-pathological parameters (phenotypic classification tumor, clinical and pathological staging, therapy and patient death) were monitored by electronic medical records. The blocks were analyzed for protein expression of PARP1 (poly ADP-ribose polymerase) and CASPASE-3 by immunohistochemical assay. Statistical analysis considered the Student's t-test for comparison of parameters (expression of PARP1 / CASPASE-3) in patients with good prognosis and with poor prognosis. Subsequently, the groups were stratified into six more risk classification criteria according to histopathological parameters, and Pearson's Chi Square test was applied in a cross-reference table for each of the six criteria. Values of P <0.05 were considered significant. Results: The evaluation of protein expression revealed increased levels of PARP1 expression in tumor tissues of patients who had a poor prognosis, compared to the levels of expression in tumors of patients with a good prognosis (P <0.0001). The evaluation of protein expression revealed decreased levels of expression of CASPASE-3 in tumor tissues of patients who had a poor prognosis, compared to the levels of expression in tumors of patients with good prognosis (P <0.0007). There was a statistically significant correlation between the highest expression of PARP1 and the patient's age at diagnosis above 70 years (p = 0.0001). Statistical significance was also found between patients belonging to the unfavorable group (according to the NCCN criteria) and higher levels of PARP1 expression (p = 0.033). However, no other significant correlations were found between the expression of PARP1 or CASPASE-3 and the other clinical-pathological parameters in question. Conclusion: In conclusion, it has been demonstrated that PARP1 and CASPASE-3 have potential as prognostic biomarkers in prostate cancer. The simultaneous analysis ofthe expression of both proteins, with roles of an antagonistic character in the context of disease outcome and progression, revealed data that corroborate the hypotheses initially proposed and are consistent with the clinical evolution of the patients. The information obtained can be both useful for the discovery of new therapeutic targets and for the development of new approaches to treatment.