Abstract
BackgroundCyclin 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.MethodsGenomic 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.ResultsBy 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).ConclusionsThe 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.
Highlights
Cyclin E is a cell cycle regulator which is critical for driving G1/S transition
Immunohistochemical characteristics and analysis of cyclin E expression By immunohistochemical analysis, high expression of cyclin E was observed in 2.3% of normal squamous mucosa (2/86), 3.7% in columnar cell metaplasia (3/81), 5.8% in Barrett’s esophagus (2/34), 19.0% in low grade dysplasia (4/21), and 35.7% in high grade dysplasia (5/14)
In this study we found that cyclin E shows a significantly higher frequency of high expression in neoplastic lesions compared to non-dysplastic tissues (Barrett’s esophagus, columnar cell metaplasia and squamous epithelium)
Summary
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. The level changes of cyclin E in esophageal adenocarcinoma and its precancerous lesion have not been well studied. Identification of early biomarkers with high sensitivity and specificity will provide physicians with valuable information for surveillance, diagnosis, prognosis, and possible treatment options for esophageal adenocarcinoma. Previous studies have suggested that esophageal adenocarcinoma develops in the following order: normal esophageal epithelium, reflux esophagitis, Barrett’s esophagus (BE), dysplasia, and esophageal adenocarcinoma [3]. During these events, a series of genetic and epigenetic aberrations contributes to the carcinogenesis, which will be potential biomarkers for early screening, surveillance and treatment of the dysplasia and adenocarcinoma
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