Cyclin E Amplification and Overexpression in Esophageal Carcinoma and Dysplasia by SNP Microarray and Immunohistochemisty Studies.
Jiqing Ye, Santhosi Bandla, Yinglin Xia, Dongfen Tan, Jeffrey Peters, Tony Godfrey, Tony Godfrey, Zhongren Zhou. University of Rochester, NY, United Kingdom; University of Rochester, NY; MD Anderson Cancer Center, Houston, TX
Background: Cyclin E, an activator of CDK2, accumulates in later G1 phase and marks the transition from G1 to S phase. It plays an important role in cell cycle progression and cell proliferation. Though a few reports have examined cyclin E expression in esophageal adenocarcinoma(EAC) and squamous cell carcinoma(SCC), the results were not consistent, and the relationship of cyclin E expression and the patients' survival is unknown.
Design: Genomic DNA were analyzed from 116 EAC patients (95 M and 21 F) using Affymetrix SNP 6.0 arrays. All analysis was done in Nexus 5.0 Copy number software. The protein expression level of cyclin E was detected by immunohistochemistry (IHC, Santa Cruz; CA) from tissue microarrays (TMA) including Barrett's esophagus (BE), low- (LGD) and high-grade dysplasia (HGD), columnar cell change (CC), squamous mucosa (SE), EAC and SCC. Patients' survival data, demographic, histological diagnoses and tumor staging data were collected. The intensity (0-3) and percentage of the cyclin E expression in TMA slides were scored by two pathologists (JY and ZZ). Fisher exact tests and Kaplan-Meier methods were used to analyze data.
Results: By genomic analysis, cyclin E1 was amplified in 19% of the EAC samples. By IHC, Cyclin E is strongly overexpressed in 15% EAC (18/117), 34% SCC (12/35), 36% HGD (5/14) and 19% LGD (4/21). However, cyclin E positivity is less than 5% in BE (2/34), CC (3/81), and SE (2/86), which usually have weak, patchy staining. The differences of cyclin E immunostaining between most neoplastic groups (including EAC, SCC, HGD and LGD) and benign groups (including BE, CC and SE) are statistically significant (p < 0.05). Interestingly, cyclin E overexpression groups in both SCC and EAC patients show better survival time than non-overexpression groups. The difference of survival time in SCC group is statistically significant (p = 0.01), but not in EAC group (p = 0.11). No association also were found between genomic amplifications and overall survival time (p=0.21) in EAC patients with genomic analysis (median follow up 26.8 months).
Conclusions: Cyclin E is significantly amplified and overexpressed in a subset of EAC patients, and significantly overexpressed in SCC, HGD and LGD patients comparing to non-dysplastic process. Cyclin E overexpression in EAC and SCC patients shows favorable prognosis. Further study is needed to explore and verify the effect of cyclin E on esophageal carcinoma.
Monday, February 28, 2011 1:00 PM
Poster Session II # 94, Monday Afternoon