Pathology of Endometrial Carcinoma
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” p
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Pathology of Endometrial Carcinoma Sigurd F. Lax
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. Keywords Endometrial carcinoma • Histopathology • Molecular pathways • Prognosis • Grading • Typing
S.F. Lax, M.D., Ph.D. (*) Department of Pathology, Hospital Graz Süd-West, Academic Teaching Hospital of the Medical University Graz, Göstingerstrasse 22, 8020 Graz, Austria e-mail: [email protected] © Springer International Publishing AG 2017 L. Hedrick Ellenson (ed.), Molecular Genetics of Endometrial Carcinoma, Advances in Experimental Medicine and Biology 943, DOI 10.1007/978-3-319-43139-0_3
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S.F. Lax
Introduction Endometrial carcinoma is the most frequent neoplasm of the female reproductive organs in the industrialized countries with the highest incidence in North America and Europe. In 2008, 288,000 new cases were diagnosed worldwide, 40,000 of them in the USA. In the same year, about 7500 women died from endometrial carcinoma in the USA [1]. The incidence rate varies significantly throughout the world with clearly lower rates in developing countries but also Japan [2]. There is also a twofold higher incidence in Caucasians compared to African Americans, but the latter seem to be affected by more aggressive tumor types [3]. These global differences in the incidence are not well understood, but there seems to be an influence of age and a so-called Western lifestyle with Western diet, high bo
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