Molecular evaluation of the corpus uteri tumors and the correlation with therapeutic response and recurrence

Abstract

Uterine body neoplasms are prevalent and exhibit a histological and diversity of growing patter. Endometrial carcinoma is the most common (90-95%) with 25% showing poor evolution, without direct correlation with prognostic factors. Studies with molecular markers and tumor genetics have shown subgroups of neoplasms with different prognoses. Uterine sarcomas make up 5% to 10% of the total and there are no consistent studies about. Expanding knowledge to define a molecular profile of these neoplasms of the uterine body can improve staging and personalize treatment, in addition to being able to guide the development of new therapies. Objectives: To evaluate the expression pattern of molecular tumor biomarkers of malignant neoplasms of the uterine body, some exploratory, and to correlate with clinical histopathological characteristics, stage, therapeutic response, recurrence and survival. Methods: a cohort study, initially retrospective, will be carried out with 130 cases attended at Unicamp between 2014 and 2019. Clinical information will be used and the blocks in paraffin of tumor tissue will be separated to assemble blocks for Tissue microarray (TMA) for immunohistochemical reactions. PTEN, CTNNB1, KRAS, FGFR-2, HER2, ARID1A, PIK3CA, P53, PMS2, MSH6, MLH1, MSH2, p16, HNF1², Napsin A, L1CAM, IMP3, SKALP / Elafina, Ki67, SOD2 and hormonal receptors (estrogen, progestogen and androgen) will be tested. The pattern of tumor lymphocyte infiltration (TIL) in H&E will be assessed. For the group of sarcomas, the calculated sample size is 54 cases, with blocks selected for TMA from 2001, and tested for desmin, smooth muscle actin, caldesmon, CD10, cyclin D1, BCOR and c-kit. This protocol will provide the background to start serum and tumor tissue deposition of new cases of women with uterine neoplasms to the institutional Biobank (CONEP B-056). Subsequently, a cohort of 214 carcinomas from the Biobank will be tested for the same described biomarkers and CA125 and HE4 serum markers to be processed at the Specialized Clinical Laboratory of CAISM. The procedures for building the TMA and the immunohistochemical reactions will be carried out at the ICESP Cancer Innovation Laboratory. The photomicrograph of the slides and counts of reagent cells will be performed at the Laboratory of Pathological Anatomy at Unicamp. The proportion of reagent cells for each marker and the serum dosages will be analyzed alone or in associations. The results will be correlated with information from clinical and tumor data, stage, the therapeutic response, relapses and survival. The Chi-square, Fisher's Exact tests and odds ratio will be calculated, with 95% confidence intervals. The interaction between variables will be analyzed by logistic regression. Survival and disease-free time will be analyzed using Kaplan-Meier curves and the Long-rank test, with Cox regression to determine the markers associated with survival. Values of p <0.05 will be significant. The budget will be presented to funding agencies. The study will start after regulatory approvals and after obtaining informed consent of the selected cases. The guidelines of Resolution 441/2012 (CNS) will be followed. (AU)