Searching for alterations in the expression of mismatch-type repair proteins (MLH1, MSH2, MSH6, and PMS2) in Prostate Cancer

• Grant number: 22/09284-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): November 01, 2022
• Effective date (End): October 31, 2023
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Kátia Ramos Moreira Leite
• Grantee: Karina Serafim da Silva
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Prostate Cancer (PCa) is the most common neoplasm in men and the second leading cause of cancer mortality. Patients are diagnosed through biopsy and receive treatment according to the aggressive potential of the neoplasm, with radical prostatectomy and radiotherapy being the treatments considered curative. Among the various causes that contribute to tumorigenesis are mutations in the mismatch repair system (MMR). The MMR system acts through 4 proteins, MSH2, MSH6, MLH1, and PMS2 that work vigilantly in DNA repair after replication and also play a role in cell cycle control and apoptosis induction. In several neoplasms, the mutational process leads to loss of protein expression and DNA repair deficiency (dMMR). The dMMR phenotype favors neoplastic development and also causes mutations in microsatellite areas causing high instability (MSI-H) and a hypermutability status. Studies have shown that metastatic PCa with dMMR or MSI-H has better response to immunotherapy based on immune checkpoint inhibitors (ICI), being the determination of this phenotype an important biomarker of response for the therapeutic decision in the management of patients with metastatic PCa. Our aim in this work is to verify the dMMR phenotype in localized CaP by immunohistochemical expression of the mismatch-like proteins, MSH2, MSH6, MLH1 and PMS2 using the Tissue Microarray (TMA) technique. The TMA was divided according to the ISUP grading system and constructed with 108 samples from patients with localized PCa treated with radical prostatectomy. Immunohistochemical expression will be correlated with major prognostic factors, biochemical relapse and overall and cancer-specific survival.