Abstract
Simple SummaryHistopathological classification of endometrial carcinoma has evidenced two main groups with different biological behavior: low-grade (G1–G2) and high-grade (G3) endometrial tumors. Moreover, the Cancer Genome Atlas (TCGA) documented four molecular 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%). The aim of the present paper is to review all endometrial carcinoma histotypes in light of the morphological and molecular prognostic TCGA groups.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.
Highlights
Type II carcinomas occur in women with no signs of hyperestrogenism and are characterized by high grade (G3), higher stage at presentation, decreased sensitivity to progestins, and poor prognosis [4]
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
The excellent prognosis of the POLEmut group is maintained across the several histotypes, justifying the guidance of the European Society of Gynaecological Oncology (ESGO)/ESTRO/European Society of Pathology (ESP) guidelines [12,23,33,34,35,43,44,52,63,64]
Summary
Endometrial carcinoma is the sixth most commonly diagnosed cancer and the 14th leading cause of cancer death in women worldwide [1] It represents the most common gynecological cancer in Europe and the USA [2,3]. Type I carcinomas occur in obese women with hyperlipidemia and signs of hyperestrogenism and are characterized by a low grade (G1–2), early stage at presentation, sensitivity to progestins, and good prognosis. Type II carcinomas occur in women with no signs of hyperestrogenism and are characterized by high grade (G3), higher stage at presentation, decreased sensitivity to progestins, and poor prognosis [4]. Nonendometrioid carcinomas, which are all graded G3 and mainly include serous endometrial carcinoma (SEC) and clear cell endometrial carcinoma (CCEC), have been considered high-risk histotypes; G3 EEC has been considered prognostically intermediate between the former and the latter [8]. The pathologic evaluation of prognostic factors is beset by challenges, including the reproducibility of histologic classification and International
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