title: 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.affiliation: Departments of Pathology and Laboratory Medicine, University of Rochester, Rochester, 601 Elmwood Ave, Box 626, Rochester, NY 14642, USA. David_zhou@urmc.rochester.edu.
authors.forename: Zhongren
authors.initials: Z
authors.lastname: Zhou
authors.forename: Santhoshi
authors.initials: S
authors.lastname: Bandla
authors.forename: Jiqing
authors.initials: J
authors.lastname: Ye
authors.forename: Yinglin
authors.initials: Y
authors.lastname: Xia
authors.forename: Jianwen
authors.initials: J
authors.lastname: Que
authors.forename: James D
authors.initials: JD
authors.lastname: Luketich
authors.forename: Arjun
authors.initials: A
authors.lastname: Pennathur
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Peters
authors.forename: Dongfeng
authors.initials: D
authors.lastname: Tan
authors.forename: Tony E
authors.initials: TE
authors.lastname: Godfrey
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001471:Barrett Esophagus / Q000235:genetics* / Q000378:metabolism; D063646:Carcinogenesis / Q000235:genetics* / Q000378:metabolism; D019927:Cyclin E / Q000235:genetics* / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011230:Precancerous Conditions / Q000235:genetics* / Q000378:metabolism; D046888:Tissue Array Analysis
chemical_list: C475820:CCNE1 protein, human; D019927:Cyclin E; D015513:Oncogene Proteins
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