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.
Wednesday, March 11, 2009 1:00 PM
Poster Session VI # 91, Wednesday Afternoon