ANALYSIS OF THE PHENOTYPE-GENOTYPE CORRELATION OF TRANSCRIPTS BRCA1, BRCA2, KI67, CSDA AND CYCLIN D1 IN PATIENTS WITH SUSPECTED PROSTATE CANCER IN THE SOUTHEAST REGION OF MATO GROSSO

Introduction: Prostate cancer (PCa) is one of the leading causes of death among men worldwide. The different histological, molecular parameters and clinical outcomes of this disease highlight its heterogeneity. The tumor suppressor genes, BRCA1 and BRCA2, as well as the Ki67, CSDA and Cyclin D1 genes, involved in the process of cell proliferation are associated with the appearance of tumors and have been used in the characterization of different neoplasms. Objectives: Correlate the anatomopathological results with the analysis of the expression of the BRCA1, BRCA2, Ki67, CSDA and Cyclin D1 genes in patients with suspected PCa in the southeast region of the state of Mato Grosso. Methods: The study of the association of phenotype-genotype included 48 patients, based on biopsies performed for anatomopathological and molecular analyses. The evaluation of the level of expression of the transcripts was performed using the Real-Time Polymerase Chain Reaction (qPCR) technique. Results: The mean age of the patients was 62.6 ±11.4 years. Anatomopathological exams showed that 45% (n=22) of patients had negative results, 16% (n=8) inconclusive and 39% (n=18) positive for Prostate Adenocarcinoma. Molecular analyses showed increased expression of Ki67 (up to 71.4%), BRCA2 (up to 100%) and BRCA1 (up to 85.71%) transcripts among patients with positive results. Among patients with inconclusive results, it was possible to determine an increase in the level of expression of Ki67 (up to 66.66%), BRCA2 (up to 66.66%) and BRCA1 (up to 83.33%) genes. When the evaluation was performed on samples from patients with negative results, less significant expression was observed in all transcripts. The CSDA and Cyclin D1 genes had increased expression in only one fragment of a patient with positive result. Most patients with biopsies classified as acinar adenocarcinoma and Gleason of 9 (5+4) and 8 (4+4) respectively, showed high levels of expression of BRCA1, BRCA2 and Ki67 transcripts, and baseline expression levels of the CSDA and Cyclin D1 genes. Conclusion: The analyses performed suggest that the markers BRCA1, BRCA2 and Ki67 could be used to indicate tissue alteration and predisposition to tumor formation, with the BRCA2 gene having the best phenotype-genotype correlation. On the other hand, CSDA and Cyclin D1 transcripts do not seem to be strongly associated with the tumor phenotype presented in this study group.