A potpourri of pathogenetic pathways in endometrial carcinoma with a focus on Lynch Syndrome

• Published in: Annals of diagnostic pathology 2019-04, Vol.39, p.92-104
• Main Authors: Wadee, Reubina, Grayson, Wayne
• Format: Article
• Language: English
• Subjects: Endometrioid endometrial carcinoma; Lynch syndrome; Microsatellite instability
• ISSN: 1092-9134; 1532-8198
• DOI: 10.1016/j.anndiagpath.2019.02.003

Endometrial carcinoma is the most frequently occurring female genital tract malignancy in developed nations, with a rising annual incidence. Endometrioid endometrial carcinoma (EEC), the most common histological variant, differs in morphologic and molecular characteristics from serous carcinomas but morphological distinction of high-grade EECs from serous carcinomas may prove difficult. Thus, molecular categorization of tumors may allow for better tumor classification with greater insight into the underlying biology of endometrial carcinomas with new therapeutic options. Microsatellite instability (MSI) is a commonly occurring molecular aberration in EECs and has been identified in most Lynch Syndrome (LS) associated tumors. This tumor syndrome predisposes afflicted individuals to a myriad of tumors including endometrial carcinoma. Herein, the molecular signature of endometrial tumors as well as LS, and its clinical manifestations are reviewed. Understanding of the pathogenetic pathways allows for greater comprehension of occurrences at a molecular level which are then appreciated at a cellular and tissue level, by the histopathologist. The molecular classification of endometrial tumors allows for further targeted therapeutic options for affected patients. Screening tests for patients with suspected LS enables surveillance of other tumors in the affected patient and her family with the potential to decrease morbidity and mortality. It is envisioned that this overview will allow for enhanced comprehension of genetic pathways by practicing pathologists, oncologists, gynecologists and other members of the multidisciplinary team, all of whom are involved in the management of the patient with an endometrial malignancy. •Molecular endometrial classification into 4 groups allows for improved targeted therapy.•Microsatellite instability is noted in most tumors associated with Lynch Syndrome.•Lynch Syndrome is diagnosed on molecular evidence of mutation of 1or more of the MMR genes.•Females with MSH6 mutation have a significant risk of developing endometrial cancer.