Monoamine oxidase as a potential target for the development of new therapeutic strategies for bladder cancer.

Abstract

e16611 Background: Bladder cancer (BC) is the most common malignancy of the urinary tract and one of the most prevalent cancers worldwide. As the overall prognosis of BC has not changed over the past 30 years, there is a pressing medical need to develop new diagnostic and therapeutic approaches. At present, efforts to deeply understand the pathogenic mechanisms that support urothelial carcinogenesis could help in identifying new therapeutic targets. Monoamine oxidases (MAOs) A and B are oxidative isoenzymes that catalyze the conversion of biogenic amines into their corresponding aldehydes and ketones through oxidative deamination. Recently, MAOs expression have been associated with metastasis and decreased overall survival in various types of cancer. However, the role of MAOs in BC is still poorly explored. This study characterized and compared the molecular profiles of MAO-A and MAO-B isoenzymes in the different histological stages of non-muscle (NMIBC) and muscle (MIBC) invasive bladder cancer, aiming the adaptation of these biomarkers as a criterion of clinical response, risk stratification and outcome prognosis. Methods: Sixty formalin-fixed paraffin-embedded samples of bladder were obtained from 34 to 96-year-old patients (mean 65 years) with BC diagnosis in University of Campinas and Paulinia Municipal Hospital/ Brazil. Subsequently, the samples were divided into 6 groups: pTis group, low-grade pTa group, high-grade pTa group, pT1 group and pT2 group; and submitted to immunohistochemistry analysis for MAO-A and MAO-B. The retrospective anonymous study was approved by the local ethics committee (Clinical Trial: RBR-6swqd2). Results: All stages and grades of NMIBC and pT2 (MIBC) showed positive immunoreactivity for both MAO-A and MAO-B. MAO-A immunoreactivities were significantly higher (p < 0.01) in the high-grade pTa, pTis and pT2 groups in relation to low-grade pTa and pT1. Likewise, MAO-B immunoreactivities were remarkably higher (p < 0.01) in the high-grade pTa and pT2 groups. No statistical differences were found between pTis and low-grade pTa for MAO-B. Interestingly, pT1 group showed the lowest (p < 0.01) MAO-A and MAO-B immunoreactivities in relation to other stages and grades of BC, probably due to disruption of the extracellular matrix, with consequent reduction in O2 delivery (hypoxia). Conclusions: These findings collectively characterize the contribution of MAOs in BC pathogenesis and suggest that MAOs have potential as a therapeutic target in BC.