[1183] Frequent CCNE1 Amplification in Uterine Serous Carcinoma and Endometrial Intraepithelial Carcinoma

Elisabetta Kuhn, Asli Bahadirli-Talbott, Ie-Ming Shih. Johns Hopkins Medical Institutions, Baltimore, MD

Background: Uterine serous carcinoma (USC) accounts for only 10% of all uterine cancers, but is the leading cause of uterus corpus cancer-related death. The pathogenesis of this aggressive neoplasm has been largely unknown until recently, when we performed a comprehensive genome-wide analysis of USC, including whole-exome sequencing and gene copy number array. Our study revealed that TP53, PIK3CA, FBXW7, PPP2R1A are the most commonly mutated genes, and CCNE1, encoding for cyclin E, is one of the most frequently amplified genes in USC. In the current study we applied fluorescence in situ hybridization (FISH) to evaluate CCNE1 copy number at a single cell resolution in USC and concurrent endometrial intraepithelial carcinoma (EIC), and correlated the molecular alterations with clinicopathological features.
Design: A total of 27 USCs and 20 concurrent EICs were collected. All the available slides were reviewed and clinicopathological features recorded. Two-color FISH assay was used to measure the gene copy number of CCNE1 in USC and EIC. The copy number was classified into six FISH strata. CCNE1 amplification was defined as the presence of loose or tight CCNE1 cluster or CCNE1 to centromeric probe ratio ≥ 2 in more than 20% of the analyzed cells. All the molecular characteristics and clinicopathological features were correlated.
Results: We found that 12 (44%) of 27 USCs and 9 (45%) of 20 EICs showed CCNE1 amplification. Overall, we found concordance in CCNE1 copy number in concurrent EIC-USC pairs (p-value <0.001). Three USCs showed intra-tumoral heterogeneity in term of CCNE1 copy number alteration, because there were tumor areas with focal CCNE1 amplification in a background of tumor without amplification. No evidence of correlation was observed between CCNE1 copy number and clinicopathological features, including age, race, clinical stage, overall survival, angiolymphatic invasion, as well as mutations in TP53, PPP2R1A, PIK3CA and FBXW7.
Conclusions: We demonstrated that amplification of CCNE1 is one of the most common molecular genetic changes in USC. CCNE1 amplification in many EICs suggests that this genetic event occurs early during tumor progression. Further studies are required to better delineate the clinical and biological impact of CCNE1 amplification on overall survival and therapy response in USC patients.
Category: Gynecologic & Obstetrics

Monday, March 4, 2013 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 178, Monday Morning

 

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