TP53 Mutation for Prediction of Tumor Recurrence and Metastasis in Bladder Cancer Patients

Abstract

Background: Bladder cancer (BC) is one of the most commonly diagnosed malignancies worldwide. Its complex etiopathogenesis is dependent on numerous risk factors that can be divided into three distinct categories: genetic and molecular abnormalities, chemical or environmental exposure and previous genitourinary disorders and family history of different malignancies. This study highlights the genetic and molecular abnormalities that considered to be part of bladder carcinogenesis such as genetic mutations of TP53. To date, cystoscopy remains the gold standard for diagnosis, butit is invasive and uncomfortable. Hence, many efforts are focusing on the development of accuratenon-invasive diagnostic tests for BC, consequently, this study aims to develop a new non-invasive and reliable test to accurately detect TP53 mutations in urine sediments of Egyptian BC patients and to evaluate the influence of their genetic status on tumor metastasis and recurrence as they are the main problems during the disease. Methods: A total of 150 BC patients and 50 healthy volunteers as controls were enrolled in this study, urine samples were obtained from all participants. DNA was extracted and TP53 mutations were examinedin exons (2+3), 4 and 5 by polymerase chain reaction (PCR). All PCR products were subjected to bidirectional sequencing. Results: Fifty four (36.0%) patients of 150 were mutated in exon (2+3) with statistically higher significant in patients when compared to controls (P = 0.001),while 96 patients(64.0%) in Exon 4, and 111 patients(74.0%) in Exon 5 with the same (P = 0.001).Moreover, a significant association was observed between TP53 status with tumor stage and grade, being alterations more common in high-stage and high-grade tumors. Conclusion: We conclude that TP53genetic mutations are independent prognostic factors for tumor metastasis and recurrence and the genetic alternation of TP53 could be used for prediction of bladder tumorigenesis.