Envolvimento do eixo Rank/Rankl/OPG em tumores penianos e sua associação com o comportamento tumoral

Abstract

Penile cancer (PC) is considered rare cancer, with a higher incidence in men over 50 years. Human papillomavirus (HPV) is one of the risk factors for the development of this disease. In recent years, new therapeutic targets have been sought for various types of cancer, including the RANK / RANKL / OPG axis, as it remains unregulated in some tumors. This study aimed to evaluate the involvement of the RANK / RANKL / OPG axis in penile tumors and its association with tumor behavior. This is a cross-sectional quantitative study of 59 penile tumors stored in the Maranhão Tumor and DNA Biobank (BTMA). Sociodemographic data were obtained through a questionnaire; clinical and histopathological data were collected through medical record analysis. Genomic DNA was extracted and performed Nested PCR for HPV identification using the primers PGMY and GP, followed by agarose gel electrophoresis. Positive samples were submitted to sequencing sangers method for viral type identification. For the expression of RANK / RANKL / OPG axis, the following steps were performed: RNA extraction and quantification, RNA-cDNA conversion using reverse transcriptase enzyme and real-time quantitative polymerase chain reaction (qPCR). It was observed that the largest number of men were over 60 years old (63.0), income up to 1 minimum wage (51%), illiterate (42.0%) and residents of municipalities in the interior state of Maranhão (59 %) and had not performed circumcision (68%). Regarding the type of lesion, ulceration was predominant, representing 36% of cases. Regarding the histological subtype, the usual was the most prevalent (33,9%). According to the classification of PC by TNM staging (T-tumor size, N - lymph nodes, M - metastasis), 23,7% corresponded to stages II and III. There was a 73% prevalence of HPV, with subtypes 16 and 11 being the most found. In the analysis of gene expression of the RANK / RANKL / OPG axis, it was observed that, in the comparison of the medians between tumor and non-tumor tissues, there was no statistically significant association. When comparing the axis with clinical characteristics, there was no significance between these variables. The association of the axis and histopathology and lesion staging showed that RANK receptor expression was associated with the occurrence of perineural invasion and with the ulcerated lesion in tumor tissue. HPV subtypes were associated with the expression of RANK and RANKL. The profile of the patients were men over 60 years of age, with low education and residing in municipalities in the interior of the state of Maranhão. The high prevalence of HPV infection in the samples may be associated with low socioeconomic status and sexual habits. RANK receptor expression was associated with the occurrence of perineural invasion, a marker of tumor aggressiveness, which may also be associated with the presence of HPV. Further studies should be performed to investigate the role of the RANK, RANKL and OPG axis in penile carcinoma, preferably using other techniques such as immunohistochemistry.