环氧合酶2与增殖细胞核抗原在家族性腺瘤性息肉病发生、发展中的作用

Effects of cyclooxygenase-2 and proliferating cell nuclear antigen on the onset and development of familial adenomatous polyposis

背景与目的:环氧合酶-2(cyclooxygenase-2,COX-2)在结直肠癌中有较高的表达,长期使用COX-2抑制剂可有效降低结直肠癌等消化道肿瘤的发病危险性。增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)是细胞异常增殖的重要标志物。本研究检测了COX-2及PCNA蛋白在正常结直肠肠黏膜、家族性腺瘤性息肉病(familial adenomatous polyposis,FAP)腺瘤和FAP癌组织中的表达,探讨COX-2在FAP肿瘤发生过程中的意义,以及与细胞增殖的关系。方法:对2004年11月至2007年7月在北京军区总医院经肠镜跟踪检查的11个FAP家系中,收集腺瘤组织36例,癌组织32例,以健康查体者结肠镜活检的正常结直肠黏膜组织34例作为对照。采用免疫组织化学染色,分别检测COX-2、PCNA的表达情况。结果:COX-2在正常结直肠黏膜、FAP腺瘤和癌组织阳性表达率分别为0%(0/34)、80.6%(29/36)、93.8%(30/32),PCNA指数分别为17.79±7.49、34.47±10.57、71.75±9.22。与正常结直肠黏膜比较,FAP腺瘤和癌组织中COX-2、PCNA表达均升高(P<0.01)。PCNA表达在FAP癌组织中显著高于FAP腺瘤(P<0.01)。FAP腺瘤中PCNA表达在COX-2阳性者显著高于COX-2阴性者(P<0.01)。结论:正常结直肠黏膜、FAP腺瘤、FAP癌组织中COX-2、PCNA表达呈逐步升高趋势,COX-2在FAP腺瘤的形成、结直肠癌发生和发展过程中起重要作用;COX-2、PCNA的检测对研究结直肠肿瘤癌前病变及干预治疗具有重要意义。

Background and Objective： Long-term use of cyclooxygenase-2 （COX-2） inhibitors can reduce the incidence of digestive cancers, such as colorectal cancers. Proliferating cell nuclear antigen （PCNA） is an important marker of cellular abnormal proliferation. This study was to evaluate the roles and correlation of COX-2 and PCNA in the onset and development of familial adenomatous polyposis （FAP） diseases. Methods. Thirty-six specimens of FAP adenomas tissues and 32 specimens of FAP carcinoma tissues from 11 FAP families, and 34 specimens of normal colonic mucosa were collected under colonoscopy from November 2004 to July 2007 in the General Hospital of Beijing Military Command. Immunohistochemistry was used to detect the expressions of COX-2 and PCNA. Results, The positive expression rates of COX-2 in normal colonic mucosa, FAP adenoma, and carcinoma tissues were 0 （0/34）, 80.6% （29/36）, and 93.8% （30/32）, respectively. Proliferation index （PI） in normal mucosa, FAP adenoma, and carcinoma tissues were 17.79±7.49, 34.47±10.57, and 71.75±9.22, respectively.Expressions of COX-2 and PCNA were significantly higher in the FAP adenoma and the carcinoma tissues than in the normal colonic mucosa （P〈 0.01）. The expression of PCNA was significantly higher in the FAP carcinoma tissues than in the FAP adenoma （P〈0.01）. The expression of PCNA was higher in the FAP adenoma tissues with positive COX-2 than in the FAP adcnorma tussues with negative COX-2 （P〈0.01）. Conclusions. COX-2 may play an important role in the development of FAP adenomas and colorectal carcinogenesis. COX-2 and PCNA may be important factors in the research on colorectal precancerous lesions and interventional therapy for colorectal neoplasm.