FasL和Caspase-3在胃癌中表达及相关免疫逃逸机制

Expressions of FasL and Caspase-3 and relevant immune escape in gastric carcinoma

目的 :研究Fas配体 (FasL)和Caspase 3表达在胃癌发生和演进中的作用。方法 :利用免疫组化方法检测FasL和Caspase 3在 113例胃癌旁上皮细胞、原发灶癌细胞和淋巴细胞以及转移灶癌细胞中的表达 ,比较原发灶癌细胞中两种蛋白表达与胃癌病理特征的关系 ,探讨原发灶癌细胞中FasL表达与原发灶癌细胞或浸润淋巴细胞中Caspase 3表达的关系。结果 :FasL在原发灶癌细胞中阳性表达率高于癌旁上皮细胞 ( 5 3 98%vs3 4 5 1% ) ,P <0 0 5 ,Caspase 3则有相反趋势 ( 3 2 74%vs 5 0 44 % ) ,P <0 0 5。70 80 %原发灶浸润淋巴细胞中Caspase 3呈阳性表达 ,显著高于原发灶癌细胞和癌旁上皮细胞中的阳性率 ,P <0 0 5。FasL在转移灶癌细胞中阳性表达率低于对应原发灶癌细胞 ( 5 1 16%vs 81 5 8% ) ,P<0 0 5 ,Caspase 3则有相反趋势 ( 5 8 14 %vs 3 4 2 1% ) ,P <0 0 5。原发灶癌细胞中FasL表达与胃癌肿块大小、浸润深度、转移、分化和lauren分型显著相关 ,P <0 0 5。原发灶癌细胞中FasL表达与其浸润淋巴细胞中Caspase 3表达呈正相关 ,P <0 0 5。结论 :FasL表达上调和Cas pase 3表达下调在胃癌发生中起到重要作用。FasL可能通过诱导浸润淋巴细胞凋亡而参与胃癌分化、浸润和转移 。

OBJECTIVE:To study the role of Fas ligand(FasL) and Caspase-3 expressions in carcinogenesis and progression of gastric cancer and the mechanism of relevant immune escape.METHODS:FasL and Caspase-3 expressions in adjacent epithelial cells,cancer cells and lymphocytes of primary foci and cancer cells of metastatic foci from 113 cases of gastric cancer were studied by immunohistochemistry.Expressions of both proteins in primary cancer cells were compared with clinicopathological features of gastric cancer,and the relationship between FasL expression in primary cancer cells and Caspase-3 expression in cancer cells or infiltrating lymphocytes of primary foci was concerned.RESULTS:Primary cancer cells more frequently expressed FasL in gastric cancers than their adjacent epithelial cells (53.98% vs 34.51%),P<0.05,while the tendency was adverse for Caspase-3 (32.74% vs 50.44%),P<0.05.Infiltrating lymphocytes of primary foci showed stronger immunoreactivity to Caspase-3 in 70.80% of gastric cancers (80/113),than that in their adjacent epithelial or cancer cells of primary foci,P<0.05.FasL was less expressed in cancer cells of metastases than in those of corresponding primary foci (51.16%,vs 81.58%),P<0.05.The tendency was adverse for Caspase-3 (58.14% vs 34.21%),P<0.05.FasL expression was significantly correlated with tumor size,invasive depth,metastasis,differentiation and Lauren's classification in primary cancer cells,P<0.05.FasL expression in primary gastric cancer cells paralleled positively with Caspase-3 expression in infiltrating lymphocytes of primary foci,P<0.05.CONCLUSIONS:Up-regulated expression of FasL and down-regulated expression of Caspase-3 in cancer cells of primary foci play an important role in gastric carcinogenesis.As an effective marker to reveal the biological behaviors,FasL is implicated in differentiation,growth,invasion and metastasis of gastric cancer by inducing apoptosis of infiltrating lymphocytes.Chemicals derived from primary foci and metastatic microenvirongment could inhibit growth of metastatic cells by regulating Caspase-3 and FasL expressions.