Fas-related apoptosis in gastric adenocarcinoma

The aims of this study were to determine whether human gastric adenocarcinomas express FasL or Fas, whether FasL expression is associated with increased apoptotic induction, especially, tumor-infiltrating lymphocyte (TIL) and whether apoptotic induction is associated with the tumor stage and histologic type. Early gastric carcinoma (EGC) (n=38) and advanced gastric carcinoma (AGC) (n=61) cases were analyzed in patients who received gastric resection from 1997 to 1998. There were 38 diffuse type and 61 intestinal type cases. Immunohistochemical staining for Fas, FasL and CD45, TACS™ in situ apoptosis detection kit, and double staining with the observation under a confocal scanning laser microscope were employed. FasL was localized to neoplastic cells in 23 cases (61%) of EGC group and 40 cases (66%) of AGC group. The extent of FasL expression was variable, with both FasL-positive and -negative neoplastic regions occurring within tumors. TILs were detected by CD45, and apoptosis of TILs as detected by co-expression of CD45 and TACS on serial histologic sections. TILs adjacent to FasL expressing tumor regions were decreased in number and TILs adjacent to FasL-negative tumor regions were increased in number; apoptotic induction of TIL showed the opposite pattern (p<0.05). Fas was expressed homogeneously throughout the tumor masses independent of the tumor stage. Fas expression in 39 cases (64%) was intestinal type and in 26 cases (68%), diffuse type. Labeling indices for tumoral apoptosis in EGC and AGC were 6.72% and 7.13%, respectively. Co-expression of FasL and Fas, which occurrs over large areas of the tumors, did not result in an enhanced rate of tumor cell apoptosis. In addition, tumor stage and other prognostic factors were not associated with Fas and FasL expressions, number of TIL and apoptotic induction. A statistically significant reduction of TILs concomitant with significantly increased TIL apoptosis adjacent to FasL-expressing regions of gastric adenocarcinomas were demonstrated. This finding suggests Fas-mediated apoptotic depletion of TIL in response to FasL expression in stomach cancers, and provides evidence to support the Fas counterattack theory as a mechanism of immune escape in gastric cancer. Furthermore, gastric carcinoma cells of the intestinal and the diffuse type did not differ in their expression of the Fas-apoptotic system.