We compared gene expression profiles from 6 esophageal adenocarcinoma and 2 normal esophageal cell lines and identified 560 differentially upregulated gene transcripts in esophageal adenocarcinoma, including several cell cycle mediators such as CDC2. CDC2 encodes p34, a cell cycle kinase subunit that regulates the G2/M transition of the cell cycle. Utilizing tissue microarrays comprised of normal esophagus (n = 20), Barrett’s esophagus (n = 10), low grade dysplasia (n = 14), high grade dysplasia (n = 22), esophageal adenocarcinoma (n = 40) and lymph node metastases (n = 19), we identified upregulation of CDC2/p34 in dysplastic and carcinomatous esophageal epithelium, as well as in lymph node metastases arising from esophageal adenocarcinoma. Examination of normal esophageal and gastric mucosa revealed baseline expression of p34 within basal and parabasal cells of the esophageal squamous epithelium and within the basally-situated proliferative zone of the gastric glands; p34 expression was not identified in superficial or apically-situated epithelial cells. Similarly, Barrett’s esophagus, an early precursor lesion in the development of esophageal adenocarcinoma, demonstrated p34 expression only within basally-situated epithelium, but not surface epithelium. In contrast, a marked upregulation of p34 surface expression was identified in 21% of low grade dysplasias and 95% of high grade dysplasias of the esophagus. Invasion and metastases of esophageal adenocarcinoma demonstrated ubiquitous expression of p34. Examination of esophageal adenocarcinoma cell lines treated with newly developed p34 inhibitors demonstrated a marked reduction in cell growth, suggesting a role for p34 in esophageal adenocarcinoma progression, as well as providing a novel immunohistochemical tool in the diagnosis of dysplastic esophageal epithelium.
[Proc Amer Assoc Cancer Res, Volume 45, 2004]