Abstracts
1998 Digestive Disease Week

#960

PROGNOSTIC VALUE OF FAS RECEPTOR AND RB PROTEIN EXPRESSION IN PATIENTS WITH ESOPHAGEAL ADENO-CARCINOMA ARISING IN BARRETT'S METAPLASIA. Domenico Coppola; Linda Mora; Robert Schreiber; William Dalton; and Richard C. Karl.

Background: Adenocarcinoma of the esophagus arising in Barrett's metaplasia (ABE) has a very poor prognosis and is increasing in incidence. In some patients Barrett's metaplasia rapidly progresses to dysplasia and carcinoma, while not in others. This management problem is compounded by sampling errors, and intra-interobserver variability in the interpretation of the degree of dysplasia. Fas receptor (FasR), and Retinoblastoma protein (Rb), are important mediators of apoptosis and tumor suppression respectively. We have previously reported that a progressive loss of Rb staining was identified as the metaplasia progressed to dysplasia and carcinoma, indicating accumulation of unstainable mutated protein. Conversely FasR stain was absent or weak in normal or metaplastic epithelium becoming detectable in the areas of high grade dysplasia and carcinoma. In this study we correlated the expression of Rb and FasR with survival of 72 patients with resected ABE.

Methods: Tumor sections from 72 patients with ABE were evaluated by immunohistochemical ABC technique. A monoclonal mouse anti-human Ab was used to identify undetermined epitopes of Rb protein (Rb-Ab5, Oncogene Science, Cambridge, MA; dilution 1:50), and monoclonal mouse anti-human Ab was used to demonstrate the 40-50 Kda FasR protein (APO-1/Fas, DAKO Corporation, Carpinteria, CA; dilution 1:5). The positive staining was quantified by CAS analysis. Results: 72 patients, 65 male and 7 female, aged 46 to 80 years, underwent surgical resection with (39%) or without (61%) radiation and chemotherapy. At follow-up, 47 of the patients were dead of disease (mean 17 months ± 12.06), and 25 were still alive (mean 23 months ± 24). Patients with either mutated Rb (10.55 mo. ± 13) or absent FasR expression (12 mo. ± 10.5) had shorter survival as compared to patients with normal Rb (25 mo. ± 16) and increased FasR expression (24 mo. ± 17). (p>0.005 respectively).

Conclusion: The detection of mutated Rb protein and/or FasR expression may identify a subset of ABE with worse prognosis. The hypothesis that Rb and FasR expression may be employed to identify patients with Barrett's esophagus prone to rapid progression to carcinoma merits evaluation in a prospective study.

Copyright 1996 - 1998, SSAT, Inc. Revised 29 June 1998.