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Pathology of Endometrial Carcinoma

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Molecular Genetics of Endometrial Carcinoma

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 943))

Abstract

On a clinicopathological and molecular level, two distinctive types of endometrial carcinoma, type I and type II, can be distinguished. Endometrioid carcinoma, the typical type I carcinoma, seems to develop through an estrogen-driven “adenoma carcinoma” pathway from atypical endometrial hyperplasia/endometrioid intraepithelial neoplasia (AEH/EIN). It is associated with elevated serum estrogen and high body mass index and expresses estrogen and progesterone receptors. They are mostly low grade and show a favorable prognosis. A subset progresses into high-grade carcinoma which is accompanied by loss of receptor expression and accumulation of TP53 mutations and behaves poorly. Other frequently altered genes in type I carcinomas are K-Ras, PTEN, and ß-catenin. Another frequent feature of type I carcinomas is microsatellite instability mainly caused by methylation of the MLH1 promoter. In contrast, the typical type II carcinoma, serous carcinoma, is not estrogen related since it usually occurs in a small uterus with atrophic endometrium. It is often associated with a flat putative precursor lesion called serous endometrial intraepithelial carcinoma (SEIC). The molecular pathogenesis of serous carcinoma seems to be driven by TP53 mutations, which are present in SEIC. Other molecular changes in serous carcinoma detectable by immunohistochemistry involve cyclin E and p16. Since many of the aforementioned molecular changes can be demonstrated by immunohistochemistry, they are useful ancillary diagnostic tools and may further contribute to a future molecular classification of endometrial carcinoma as recently suggested based on The Cancer Genome Atlas (TCGA) data.

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  1. Department of Pathology, Hospital Graz Süd-West, Academic Teaching Hospital of the Medical University Graz, Göstingerstrasse 22, 8020, Graz, Austria

    Sigurd F. Lax M.D., Ph.D.

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Correspondence to Sigurd F. Lax M.D., Ph.D. .

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  1. Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York, USA

    Lora Hedrick Ellenson

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© 2017 Springer International Publishing AG

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Lax, S.F. (2017). Pathology of Endometrial Carcinoma. In: Hedrick Ellenson, L. (eds) Molecular Genetics of Endometrial Carcinoma. Advances in Experimental Medicine and Biology, vol 943. Springer, Cham. https://doi.org/10.1007/978-3-319-43139-0_3

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