[668] Mitosin Expression Is a Biomarker of Cancer Progression in Barrett's Esophagus

G Soucy, DP Coco, JL Hornick, Q Huang, RD Odze. Brigham and Women's Hospital, Boston; Veterans Administration Hospital, Boston

Background: Molecular markers of cancer development in Barrett's esophagus (BE) include 17p (p53) LOH, tetraploidy and aneuploidy. We have previously identified a more than 5-fold increase in the expression of mitosin (CENPF) by mRNA microarray in p53 -/- tetraploid (G2/4N) epithelial cell strains established from BE biopsies (Barrett et al. Cancer Res 15:63 (14):4211-7). Mitosin is a nuclear matrix protein that plays a major role in chromosome segregation during mitosis and is, thus, important for cell cycle control. The aim of this study was to evaluate mitosin as a biomarker of cancer progression in BE by comparing its expression in patients who progressed to dysplasia / cancer, versus those who did not, over the course of long-term endoscopic surveillance.
Design: Routinely processed non-dysplastic index biopsies of 46 BE patients (M/F ratio: 35/11, mean age: 56 years), consisting of 19 patients who progressed to dysplasia (N=6) or cancer (N=13) over the course of long-term surveillance (mean follow-up = 58.3 months; range 13 - 160 months) and 27 patients who did not develop dysplasia or cancer upon follow-up (mean follow-up = 123.9 months; range 35 - 226 months) were immunohistochemically stained for mitosin and evaluated in a blinded fashion for the mean number of positive cells per crypt in each biopsy specimen. Comparisons were made between progressors and non-progressors, and also between the subgroups of dysplasia and cancer progressors.
Results: BE progressors showed significantly increased mitosin expression in index biopsies (mean # positive cells/crypt =17.5 +/- 5.5) versus non-progressors (14.2 +/- 5.9, p=0.04). Of the neoplasia progressors, there was no significant difference in expression between patients who developed cancer compared to those who only progressed to dysplasia (low or high-grade). When only patients who progressed to cancer (n=13) were compared to non-progressors, the mitosin grade remained significantly higher in the former (17.6 +/- 5.6) compared to the latter (14.2+/-5.9, p=0.05).
Conclusions: Mitosin is involved in the pathogenesis of cancer in BE and overexpression may represent a potentially valuable biomarker in patients with this disorder. Further prospective studies on larger cohorts of BE patients should be performed in order to further evaluate this finding.
Category: Gastrointestinal

Wednesday, March 11, 2009 1:00 PM

Poster Session VI # 91, Wednesday Afternoon