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KMID : 0377220000250010009
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Medical Journal of Chosun Univercity
2000 Volume.25 No. 1 p.9 ~ p.22
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Fas-related apoptosis in gastric adenocarcinoma
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Lim Sung-Chul
Hwang Chul-Kee
Oh Seo-Jin
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Abstract
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Background and Objectives : The purpose of this study is to determine whether human gastric adenocarcinomas express Fas-L, sFas-L or Fas , whether serum sFas-L leyel is changed in gastric cancer patients after gastrectomy, whether Fas-L expression is associated with increased apoptotic induction, especially, tumor-infiltrating Iymphocytes(TIL) and whether apoptotic induction is associated with the tumor stage and histologic type.
Materials and Methods : The author analysed 38 cases of early gastric carcinoma(EGC) and 61 cases of advanced gastric carcinoma (AGC) which received gastric resection from 1997 to 1998. Of them, the number of diffuse type is 38 cases and the number of intestinal type is 61 cases. The author used immunohistochemical staining for Fas, Fas L and CD45, TACS^TM in situ apoptosis detection kit, and sFas ligand ELISA kit.
Results : Fas-L was localized to neoplastic cells in 23 cases (23/38; 61%) of EGC group and 40cases (40/61; 66%) of AGC group. The extent of Fas-L expression was variable, with both Fas-L was localized to neoplastic cells in 23 cases (23/38; 61%) of EGC group and 40 cases(40/61; 66%) of group. The extent of Fas-L expression was variable, with both FasL-positive and negative neoplastic region cccuring within. TIL were detected by co-expression of CD4S and TACS on serial histologic sections. TIL adjacent to Fas-L erxressing tumor regions were decreased in number and TIL adjacent to FasL-negative tumor regions were increased in number; apoptotic induction of TIL showed the opposite pattern (p<05). Fas expression was found essentially homogeneously throughout the tumor mass independent of tumor stage. Fas expression showed 39 cases (39/61; 64%) of intestinal type and 26 cases (26/38; 68%) of diffuse type. Labeling indces for tumoral apoptosis in EGC and AGC were 6.72% and 7.13%, respectively and this difference was statistically insignificant. Co-expression of Fas-L and Fas, which occurred over large areas of the tumors, did not result in an enhanced rate of tumor cell apoptosis. The mean serum sFas-L level was significantly higher in patients before treatment compared with controls, whereas in post-gastrectomy patients, it was significantly lower, In addition, tumor stage and other prognostic factors were not associated with Fas and Fas-L expression, serum sFas-L level, number of TIL and apoptotic induction.
Conclusion: ’The author demonstrates a statistically significant reduction of TIL concomitant with significantly increased TIL apoptosis adjacent to FasL-expressing regions of gastric adenocarcinomas. Also an elevated level of ·serum sFas-L in the gastric adenocarcinoma group was noted. These findings suggest Fas-mediated apoptotic depletion of TIL in response to Fas-L expression by stomach cancers, and provide the evidence to support the Fas counter-attack as a mechanism of immune escape in gastric cancer. And These findings indicate that the serum sFas-L level is a useful indicator in evaluating postoperative follow-up. In addition, gastric carcinoma cells of the intestinal and diffuse type did not differ in their expression of the Fas-apoptotic system.
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KEYWORD
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Fas-related apoptosis, Gastric adenocarcinoma, Fas, Fas-L, sFas-L
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