Immunohistochemistry and molecular classification of endometrial adenocarcinomas with heterogeneous expression of DNA mismatch repair genes

• Grant number: 19/03197-6
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2019
• End date: October 31, 2021
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Louise de Brot Andrade
• Grantee: Louise de Brot Andrade
• Host Institution: A C Camargo Cancer Center. Fundação Antonio Prudente (FAP). São Paulo , SP, Brazil
• Associated researchers: Alexandre André Balieiro Anastácio da Costa ; Dirce Maria Carraro ; Giovana Tardin Torrezan ; Glauco Baiocchi Neto

Abstract

Endometrial adenocarcinoma is classified by the Bokhman system in type I and II based on clinical and epidemiological observations, being type I, low-grade tumors and type II tumors to high grade. A classification based on histological aspects and molecular profile have been proposed. The TCGA (The Cancer Genome Atlas) identified four molecular groups of endometrial adenocarcinoma: (1) mutations in POLE ("ultramutaded" phenotype), (2) "high copy number" (mutations in TP53), (3) "low number of copies "in which the tumors do not exhibit any of the changes described in the other types and (4) tumors with a predominance of microsatellite instability. In a small number of patients, heterogeneous labeling is observed in the loss of protein expression for mismatch repair. Objectives: Immunohistochemical study and molecular classification of endometrial adenocarcinoma cases with heterogeneous loss of protein expression of DNA repairing genes and comparison of these areas. Cases and Methods: A retrospective cohort study with approximately 500 patients with endometrial adenocarcinoma at the A.C.Camargo Cancer Center from 2007 to 2017. It is expected to identify about 30 patients with heterogeneous expression of DNA repairing genes. After review and morphological classification, the DNA repairing gene proteins will be investigated through immunohistochemistry, which will be microdissected for separation of the heterogeneous areas, which will follow with POLE sequencing, immunohistochemistry for p53 and methylation of promoters of repair genes with loss of expression. (AU)