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Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc

Frequent CCNE1 amplification in endometrial intraepithelial carcinoma and uterine serous carcinoma.


PMID 24309323

Abstract

Uterine serous carcinoma accounts for only 10% of all uterine epithelial cancers, but is the leading cause of death among them. The pathogenesis of this aggressive neoplasm has been largely elusive until recently, when comprehensive genome-wide analyses of uterine serous carcinoma have been performed. Among amplified cancer-related genes, CCNE1, encoding for cyclin E1, is frequently amplified in uterine serous carcinoma. In the current study we applied fluorescence in situ hybridization (FISH) to determine CCNE1 copy number in uterine serous carcinoma and concurrent endometrial intraepithelial carcinoma, the noninvasive component of uterine serous carcinoma, and the results were correlated with clinicopathological and molecular features. We found that 20 (45%) of 44 uterine serous carcinomas and 11 (41%) of 27 endometrial intraepithelial carcinomas showed CCNE1 amplification. Overall, we found high concordance in CCNE1 copy number in concurrent uterine serous carcinoma and endometrial intraepithelial carcinoma pairs (P-value=0.0003). No correlation was observed between CCNE1 copy number and clinicopathological features, as well as common mutations previously reported in uterine serous carcinoma. In summary, we confirm that amplification of CCNE1 is a frequent molecular genetic change in uterine serous carcinoma. Moreover, the identification of CCNE1 amplification in many endometrial intraepithelial carcinomas suggests that this genetic event occurs early during tumor progression.