尿素循环限速酶CPS1在胃黏膜肠上皮化生及癌变过程中的表达特征

Expression of CPS1 in gastric intestinal metaplasia and subsequent carcinogenesis

目的探讨尿素循环限速酶氨甲酰磷酸合成酶1(CPS1)在胃黏膜肠上皮化生及癌变过程中的表达特征。方法采用免疫组织化学法检测10例胃浅表黏膜慢性炎、10例小肠黏膜慢性炎、10例结肠黏膜慢性炎、32例慢性萎缩性胃炎伴肠化生、30例低度异型增生、32例高度异型增生中CPS1、CDX2的表达及172例肠型胃癌组织芯片中CPS1的表达。结果CPS1和CDX2在胃黏膜中均无阳性表达。CDX2在小肠、结肠黏膜中均呈阳性表达,而CPS1仅在小肠黏膜中表达。CPS1强阳性表达率在肠化生占100%(32/32),低度异型增生占70.0%(21/30),高度异型增生占12.5%(4/32),肠型胃癌占8.1%(14/172)。CPS1的表达率在癌变各个阶段间差异有统计学意义(P<0.05)。CDX2在肠化生、低度异型增生、高度异型增生中强阳性表达率为87.5%(28/32)、100%(30/30)和78.1%(25/32)。CDX2在低度异型增生、高度异型增生间差异有统计学意义(P=0.0118)。在胃腺癌中,CPS1表达下调与浸润深度和TNM分期显著相关。结论本研究支持CPS1和CDX2均是鉴别胃黏膜肠上皮化生病变的特异性标志物;与CDX2相比,CPS1在高度异型增生及腺癌阶段表达下调,提示CPS1表达下调可能是肠化生恶性转变的标志物;CPS1表达下调与临床分期呈正相关,提示CPS1可能是肠型胃癌的抑癌基因。

Objective To investigate the expression characteristics of CPS1 in gastric intestinal metaplasia and carcinogenesis.Methods Retrospective tissues were obtained from chronic superficial gastritis(n=10),chronic inflammation of small intestinal mucosa(n=10),chronic inflammation of colon mucosa(n=10),intestinal metaplasia(n=32),low-grade dysplasia(n=30),high-grade dysplasia(n=32),and gastric cancer(n=172).Standardized immunohistochemistry for CPS1,CDX2 was performed followed by quantitative staining and statistical analysis.Results There was no positive expression of CPS1 and CDX2 in gastric mucosa.CDX2 was positive in small intestine mucosa and colon mucosa.Differ from CDX2,CPS1 was negative in colonic mucosa.The positive rate of CPS1 was 100%(32/32)in intestinal metaplasia,70.0%(21/30)in low-grade dysplasia,12.5%(4/32)in high-grade dysplasia and 8.1%(14/172)in gastric adenocarcinoma.There were significant differences in the expression rate of CPS1 among different stages of carcinogenesis(P<0.05).The strong positive rates of CDX2 were 87.5%(28/32)in intestinal metaplasia,100%(30/30)in low-grade dysplasia and 78.1%(25/32)in high-grade dysplasia.There was significant difference in CDX2 expression between low-grade dysplasia and high-grade dysplasia(P=0.0118).In gastric adenocarcinoma,the down-regulated CPS1 expression was positively correlated with depth of infiltration and TNM stage.Conclusion Both CPS1 and CDX2 are specific markers to discriminate intestinal metaplasia.Compare to CDX2,CPS1 is down-regulation rapidly in the stage of high-grade dysplasia and adenocarcinoma,suggesting that the down-regulation of CPS1 may be a marker of malignant transformation of intestinal metaplasia.Down-regulation of CPS1 was positively correlated with clinical stages,suggesting that CPS1 may be a tumor suppressor gene of intestinal-typed gastric cancer.