Association of molecular subgroups with pathological parameters in endometrial carcinomas.

Background: The integration of molecular features into the already existing pathological classification of endometrial carcinomas will offer significant prognostic information. As the literature search reveals, there are no studies from India that have classified these carcinomas based on molecular subtypes. The aim of the study was to classify endometrial carcinomas into four subtypes based on their molecular and immunohistochemical features and to find out the association of each of these molecular subtypes with the other pathological parameters.

Methods: A prospective study was done on 37 consecutive cases of fresh hysterectomy specimens, biopsy-proven as endometrial carcinomas between November 2019 and August 2020. Three immunohistochemical markers ( p53 , mismatch repair proteins, MutS homolog6 and Postmeiotic seggregation 2 respectively[ MSH6 , and PMS2] ), along with DNA (deoxyribonucleic acid) sequencing of selected regions of the POLE gene was performed in each of the 37 cases. Endometrial carcinomas were subclassified into four subtypes, and the association of each of these four subtypes with the other pathological parameters was also explored. Statistical analysis was done using the IBM Statistical Package for the Social Science (SPSS) Version 20.0 software (IBM SPSS, USA).

Results: Among the 37 cases studied, eight (21.6%) cases were p53 abnormal, eight (21.6%) cases showed MMR-D (mismatch repair deficient), one case (2.7%) showed mutation of POLE , and 21 cases (56.8%) were assembled under p53 wild-type. Higher grade endometrial carcinomas showed more (80.0%) p53 abnormal ( P < 0.001). All the p53 wild-type (100%) were of Type 1 endometrial carcinoma subtype ( P = 0.001) and low-grade type (90.5%; P = 0.005).

Conclusion: Our study confirms that the type of carcinoma and grade correlates with p53 expression, p53 abnormal being associated with higher grade and type 2 endometrial carcinomas, whereas p53 wild-type is associated with low-grade and type 1 endometrial carcinoma. There was only one case of the POLE subtype identifiable in our study.