Overexpression of Fas ligand (FasL) during malignant transformation in the large bowel and in Barrett's metaplasia of the esophagus

Esophageal and colorectal adenocarcinomas overexpress Fas ligand (FasL),which can protect them from immune surveillance. The aim of this work was to determine whether Fast expression, and therefore FasL-dependent immune evasion, occurs early during malignant transformation in Barrett's metaplasia (BM) of the esophagus, and in the large intestine. Sections of formalin-fixed and paraffin-embedded tissue from esophageal and large bowel biopsies and resection specimens were immunostained for Fast using standard immunoperoxidase technique. The percentage of positive cells was correlated with the degree of dysplasia in BM and with the size and villous architecture of colorectal adenomas. In BN, Fast was detected in 55% of cases negative for dysplasia, and was associated with inflammation in almost all positive cases. By contrast, all cases of BM (100%) with low or high-grade dysplasia were FasL-positive. In the large intestine, 25% of small adenomas were negative for Fast, and Fast overexpression was significantly more frequent in larger adenomas and in adenomas with tubulovillous or villous morphology. Our results suggest that (1) Fast overexpression is acquired early during malignant transformation of BM and the large bowel and (2) Fast overexpression occurs relatively earlier during malignant progression of BM than the large bowel, probably as a result of the preceding repeated inflammation. Copyright (C) 1999 by W.B. Saunders Company.