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Molecular genetic pathways in various types of endometrial carcinoma: from a phenotypical to a molecular-based classification

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Abstract

Two types of endometrial carcinoma are distinguished with respect to biology and clinical course. Type-I carcinoma is related to hyperestrogenism by association with endometrial hyperplasia, frequent expression of estrogen and progesterone receptors and younger age, whereas type-II carcinoma is unrelated to estrogen, associated with atrophic endometrium, frequent lack of estrogen and progesterone receptors and older age. Histologically, endometrioid and mucinous carcinomas are considered type I, serous and clear cell carcinomas type II. Molecular data from multiple studies support the hypothesis of different genetic pathways in the development of endometrioid and serous carcinoma. The most frequent genetic alteration in endometrioid carcinoma is PTEN inactivation by mutation, followed by microsatellite instability (MIN) and mutations of K-ras and β-catenin. PTEN and K-ras mutations and MIN are considered early events, occurring in a subset of atypical endometrial hyperplasia, whereas p53 mutation is considered a late event, during progression of about 10–20% of endometrioid carcinomas. In serous carcinoma, p53 mutation is the most frequent genetic alteration, followed by inactivation of p16 and e-cadherin and amplification of her2/neu. p53 mutation occurs in endometrial intraepithelial carcinoma, the putative precursor of serous carcinoma. Considering these genetic pathways, the current histological classification of endometrial carcinoma is molecular based.

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Acknowledgements

The author is dedicating this article to his distinguished teachers in gynecological pathology and molecular pathology, Drs. Robert J. Kurman and Lora H. Ellenson.

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Correspondence to Sigurd F. Lax.

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Lax, S.F. Molecular genetic pathways in various types of endometrial carcinoma: from a phenotypical to a molecular-based classification. Virchows Arch 444, 213–223 (2004). https://doi.org/10.1007/s00428-003-0947-3

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  • DOI: https://doi.org/10.1007/s00428-003-0947-3

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