New Pathological and Clinical Insights in Endometrial Cancer in View of the Updated ESGO/ESTRO/ESP Guidelines

Abstract

Endometrial carcinoma represents the most common gynecological cancer in Europe and the USA. Histopathological classification based on tumor morphology and tumor grade has played a crucial role in the management of endometrial carcinoma, allowing a prognostic stratification into distinct risk categories, and guiding surgical and adjuvant therapy. In 2013, The Cancer Genome Atlas (TCGA) Research Network reported a large scale molecular analysis of 373 endometrial carcinomas which demonstrated four categories with distinct clinical, pathologic, and molecular features: POLE/ultramutated (7% of cases) microsatellite instability (MSI)/hypermutated (28%), copy-number low/endometrioid (39%), and copy-number high/serous-like (26%). In the present article, we report a detailed histological and molecular review of all endometrial carcinoma histotypes in light of the current ESGO/ESTRO/ESP guidelines. In particular, we focus on the distribution and prognostic value of the TCGA groups in each histotype.

Keywords: CTNNB1; TCGA; clear cell carcinoma; endometrial carcinoma; prognosis; serous carcinoma; undifferentiated carcinoma.

Figure 1

Distribution of TCGA molecular groups according to endometrial carcinoma histotype.

Figure 2

Molecular landscape of endometrial carcinoma: the role of the immunohistochemical surrogates. (A,B) Dedifferentiated carcinoma with mismatch repair deficiency. (C,D) Serous carcinoma with abnormal p53 expression. (E,F) Endometrioid carcinoma with nuclear beta-catenin accumulation. (G,H) Endometrioid carcinoma with positivity for L1CAM in >10% of tumor cells (H&E, LSAB, 10×).