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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.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
PIMENTA, RUAN; CAMARGO, JULIANA A.; GONCALVES, GUILHERME L.; GHAZARIAN, VITORIA; CANDIDO, PATRICIA; GUIMARAES, VANESSA R.; ROMAO, POLIANA; CHIOVATTO, CAROLINE; DA SILVA, KARINA SERAFIM; DOS SANTOS, GABRIEL A.; et al. Overexpression of miR-17-5p may negatively impact p300/CBP factor-associated inflammation in a hypercholesterolemic advanced prostate cancer model. MOLECULAR BIOLOGY REPORTS, v. 50, n. 9, p. 13-pg., . (18/26528-5, 18/19906-3, 19/19138-9, 22/09284-0, 19/00156-7, 21/02341-6, 20/01317-1)
PIMENTA, RUAN; MIOSHI, CAROLINA MIE; GONCALVES, GUILHERME L.; CANDIDO, PATRICIA; CAMARGO, JULIANA A.; GUIMARAES, VANESSA R.; CHIOVATTO, CAROLINE; GHAZARIAN, VITORIA; ROMAO, POLIANA; DA SILVA, KARINA SERAFIM; et al. Intratumoral Restoration of miR-137 Plus Cholesterol Favors Homeostasis of the miR-137/Coactivator p160/AR Axis and Negatively Modulates Tumor Progression in Advanced Prostate Cancer. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 24, n. 11, p. 16-pg., . (18/26528-5, 18/19906-3, 19/19138-9, 22/09284-0, 19/00156-7, 21/02341-6, 20/01317-1)

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