Lim Sung-Chul
Department of Pathology, College of Medicine, Chosun University, Kwangju, South Korea.
Oncol Rep. 2003 Jan-Feb;10(1):57-63.
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 trade mark 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.
本研究的目的是确定人类胃腺癌是否表达FasL或Fas，FasL表达是否与凋亡诱导增加相关，尤其是肿瘤浸润淋巴细胞（TIL），以及凋亡诱导是否与肿瘤分期和组织学类型相关。对1997年至1998年接受胃切除术的患者中的早期胃癌（EGC）（n = 38）和进展期胃癌（AGC）（n = 61）病例进行分析。其中有38例弥漫型和61例肠型病例。采用Fas、FasL和CD45的免疫组织化学染色、TACS商标原位凋亡检测试剂盒以及共聚焦扫描激光显微镜下观察的双重染色。FasL定位于EGC组23例（61%）和AGC组40例（66%）的肿瘤细胞中。FasL表达程度各异，肿瘤内同时存在FasL阳性和阴性的肿瘤区域。通过CD45检测TIL，并在连续组织切片上通过CD45和TACS的共表达检测TIL的凋亡。与FasL表达肿瘤区域相邻的TIL数量减少，而与FasL阴性肿瘤区域相邻的TIL数量增加；TIL的凋亡诱导呈现相反模式（p<0.05）。Fas在整个肿瘤块中均匀表达，与肿瘤分期无关。39例（64%）Fas表达为肠型，26例（68%）为弥漫型。EGC和AGC中肿瘤细胞凋亡的标记指数分别为6.72%和7.13%。FasL和Fas在肿瘤大片区域的共表达并未导致肿瘤细胞凋亡率升高。此外，肿瘤分期和其他预后因素与Fas和FasL表达、TIL数量及凋亡诱导均无关。证实胃腺癌FasL表达区域附近TIL显著减少，同时TIL凋亡显著增加。这一发现提示Fas介导的TIL凋亡消耗是对胃癌中FasL表达的反应，并为支持Fas反击理论作为胃癌免疫逃逸机制提供了证据。此外，肠型和弥漫型胃癌细胞在Fas凋亡系统的表达上没有差异。
