Cyclin E involved in early stage carcinogenesis of esophageal adenocarcinoma by SNP DNA microarray and immunohistochemical studies.

Abstract

BACKGROUND:

Cyclin E is a cell cycle regulator which is critical for driving G1/S transition. Abnormal levels of cyclin E have been found in many cancers. However, the level changes of cyclin E in esophageal adenocarcinoma and its precancerous lesion have not been well studied. Here, we focus on the gene amplification and expression of cyclin E in these lesions, and aim to ascertain the relationship with clinicopathological characteristics.

METHODS:

Genomic DNA was analyzed from 116 esophageal adenocarcinoma and 26 precancerous lesion patients using Affymetrix SNP 6.0 arrays. The protein overexpression of cyclin E was also detected using immunohistochemistry from tissue microarrays containing esophageal adenocarcinoma and precancerous lesions. Patient survival and other clinical data were collected and analyzed. The intensity and percentage of the cyclin E expressing cells in tissue microarrays were scored by two pathologists. Fisher exact tests and Kaplan-Meier methods were used to analyze data.

RESULTS:

By genomic analysis, cyclin E was amplified in 19.0% of the EAC samples. By immunohistochemistry, high expression of cyclin E was observed in 2.3% of squamous mucosa tissues, 3.7% in columnar cell metaplasia, 5.8% in Barrett's esophagus, 19.0% in low grade dysplasia, 35.7% in high grade dysplasia, and 16.7% in esophageal adenocarcinoma. The differences in cyclin E high expression between neoplastic groups and non-dysplasia groups are statistically significant (p < 0.05). The prognosis for patients with high cyclin E expression appeared slightly better than for those with low cyclin E expression although this was not statistically significant (p = 0.13).

CONCLUSIONS:

The expression of cyclin E significantly increases from non-dysplasia esophageal lesion to low and high grade dysplasia, suggesting that cyclin E plays an important role in the early stage of carcinogenesis. Importantly, cyclin E is also amplified and highly expressed in a subset of esophageal adenocarcinoma patients, but this increase is not associated with worse prognosis.

• Authors: Zhongren Zhou, Santhoshi Bandla, Jiqing Ye, Yinglin Xia, Jianwen Que, James D Luketich, Arjun Pennathur, Jeffrey H Peters, Dongfeng Tan, Tony E Godfrey
• Journal: BMC gastroenterology (BMC Gastroenterol) Vol. 14 Pg. 78 (Apr 17 2014) ISSN: 1471-230X [Electronic] England
• PMID: 24742107 (Publication Type: Journal Article)

Chemical References

• CCNE1 protein, human
• Cyclin E
• Oncogene Proteins

Topics

• Adenocarcinoma (genetics, metabolism)
• Adult
• Aged
• Aged, 80 and over
• Barrett Esophagus (genetics, metabolism)
• Carcinogenesis (genetics, metabolism)
• Cyclin E (genetics, metabolism)
• Esophageal Neoplasms (genetics, metabolism)
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Immunohistochemistry
• Male
• Middle Aged
• Oligonucleotide Array Sequence Analysis
• Oncogene Proteins (genetics, metabolism)
• Polymorphism, Single Nucleotide
• Precancerous Conditions (genetics, metabolism)
• Tissue Array Analysis