Molecular genetic pathways in various types of endometrial carcinoma: from a phenotypical to a molecular-based classification
- 1 March 2004
- journal article
- review article
- Published by Springer Science and Business Media LLC in Virchows Archiv A Pathological Anatomy and Histopathology
- Vol. 444 (3), 213-223
- https://doi.org/10.1007/s00428-003-0947-3
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 beta-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.Keywords
This publication has 100 references indexed in Scilit:
- Hypermethylation in promoter region of E‐cadherin gene is associated with tumor dedifferention and myometrial invasion in endometrial carcinomaCancer, 2003
- The Outcome of Stage I–II Clinically and Surgically Staged Papillary Serous and Clear Cell Endometrial Cancers When Compared with Endometrioid CarcinomaGynecologic Oncology, 2000
- hMLH1 Promoter Hypermethylation Is an Early Event in Human Endometrial TumorigenesisThe American Journal of Pathology, 1999
- Mutations of the β‐Catenin Gene in Endometrial CarcinomasJapanese Journal of Cancer Research, 1999
- Detection of DNA gains and losses in primary endometrial carcinomas by comparative genomic hybridizationGenes, Chromosomes and Cancer, 1997
- K-rasPoint Mutations in Endometrial Carcinoma: Effect on Outcome Is Dependent on Age of PatientGynecologic Oncology, 1996
- Case--Control Study of Endogenous Steroid Hormones and Endometrial CancerJNCI Journal of the National Cancer Institute, 1996
- Life‐time risk of different cancers in hereditary non‐polyposis colorectal cancer (hnpcc) syndromeInternational Journal of Cancer, 1995
- Hereditary aspects of endometrial adenocarcinomaInternational Journal of Cancer, 1995
- Mutation and allelic loss of the p53 gene in endometrial carcinoma. Incidence and outcome in 92 surgical patientsCancer, 1995