Surface Mitoses Are a Predictor of Cancer Progression in Barrett's Esophagus
DP Coco, A Srivastava, CA Sanchez, X Li, D Cowan, BJ Reid, PL Blount, RD Odze. Brigham and Women's Hosptial, Boston, MA; Dartmouth Hitchcock Medical Center, Lebanon, NH; Fred Hutchinson Cancer Center, Seattle, WA; University of Washington, Seattle, WA
Background: At present, dysplasia is the most reliable biomarker of cancer progression in patients with Barrett's esophagus (BE). However, dysplasia interpretation suffers from a high degree of interobserver variability, and only a small proportion of BE patients develop this morphologic alteration. Cell cycle abnormalities and increased cell proliferation have been linked to cancer in BE. In a previous preliminary study, we reported an association between the presence of surface mitoses and progression to adenocarcinoma in BE. The aim of this study was to evaluate the prognostic significance of mitoses in a large prospective cohort of BE patients with long-term follow-up.
Design: 1752 routinely processed mucosal biopsies from 101 BE patients (M/F ratio: 85/16, mean age: 63.3 years, mean BE segment length 5.4 cm), followed for a mean of 85.5 months (5.8-158.4 months), all of whom had a baseline index endoscopy between 1995 and 1999 and at least 1 follow-up endoscopy, were included. The development of adenocarcinoma was the primary outcome variable. All biopsies were evaluated, in a blinded fashion, for number of mitoses within dysplastic and non-dysplastic epithelium. Data was analyzed using a Cox regression model to account for follow-up intervals and censored data.
Results: A strong positive correlation was noted between the presence of surface mitoses (both typical and atypical) and the development of adenocarcinoma (p<0.0001, hazard ratio [HR]: 5.0, 95% CI 4.0-6.3). The presence of atypical mitoses (surface and crypt) was also a predictor of progression (p<0.0001, HR: 2.9, 95% CI 2.1-4.3). Specifically, within this group, atypical surface mitoses had the strongest correlation (p<0.0001, HR: 3.6, 95% CI 2.2-5.9). No significant correlation was noted between crypt mitoses and the development of adenocarcinoma.
Conclusions: Surface epithelium mitoses are a valuable morphologic biomarker of progression to cancer in BE. This is consistent with the previously well-known association between increased proliferation, cell cycle abnormalities and cancer progression in BE. (Supported by NIH P01CA91955).
Wednesday, March 11, 2009 1:00 PM
Poster Session VI # 90, Wednesday Afternoon