Molecular characterization of gleason pattern 5 and ductal histologic variant Prostate Cancer

• Grant number: 22/15537-9
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2023
• End date: August 31, 2025
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Kátia Ramos Moreira Leite
• Grantee: Kátia Ramos Moreira Leite
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Ruan César Aparecido Pimenta ; Sabrina Thalita dos Reis Faria ; William Carlos Nahas

Abstract

In a pilot study, we identified pathogenic variants of uncertain significance and missense variants in representative cases of Gleason pattern 5 and ductal histologic variant, many related to actionable pathways from a therapeutic standpoint. Our purpose for this project is to validate the molecular characterization of pattern 5 and ductal histological variant, which are known to behave more aggressively. To do this we will perform a quantitative analytical experimental study to validate molecular markers by immunohistochemical techniques and mutation analysis. Surgical specimens from patients undergoing radical prostatectomy for the treatment of localized prostate cancer presenting Gleason 5 and/or ductal pattern will be studied for the presence of mutations by NGS and immunohistochemical expression of proteins encoded by tumor suppressor genes, mTOR pathway controllers, related to chromatin organization, DNA repair and control of the androgen pathway identified in our preliminary study and described as frequently mutated and related to PCa progression. (AU)