胃泌素和COX-2在结肠腺瘤中的表达及意义

The Expression of Gastrin and Cyclooxygenase-2 in Colorectal Adenoma and Its Significance

  • 摘要: 目的: COX-2高表达与肿瘤发生的密切关系被多数学者证实,并且非甾体消炎药已被用来预防或治疗结肠多发息肉和结肠癌。GAS除了促进胃粘膜生长外,亦发现对结肠粘膜细胞的生长有刺激作用,而且近年研究表明GAS的这种促生长作用与COX-2的表达密切相关。本文旨在探索GAS、COX-2的表达与结肠腺瘤性息肉组织增殖、分化以及是否恶变之间的联系。 方法: 回顾性收集2003年6月~2006年6月间遵义医学院附属医院行结肠镜下息肉切除、外科手术和取病理活检的息肉标本,结合其临床资料,共获取腺瘤性息肉标本68例,另选10例非腺瘤性息肉和15例肠镜检查未见异常的肠粘膜组织作为正常对照组。所有患者均无家族性腺瘤病史和结肠癌史,均未长期服用过非甾体抗炎药(NSAIDs)、质子泵抑制剂或糖皮质激素。通过免疫组化染色,观察不同组织学类型、不同异型增殖程度以及有无局部恶变时息肉中GAS、COX-2的表达情况,以Ki-67的表达情况作为判断组织增殖程度的指标。 结果: GAS、COX-2在正常肠粘膜及非腺瘤息肉中呈弱阳性表达或不表达,在绒毛腺瘤、重度异型增生及腺瘤局部恶变时高表达。其表达与组织类型和异型增生程度均有直线相关性(P<0.01)。COX-2的阳性表达与GAS表达相关(r=0.67,P<0.01)。Ki-67表达在GAS或COX-2增高时亦增高,特别在GAS和COX-2共同表达时增加明显。 结论: GAS、COX-2的表达在绒毛腺瘤、重度异型增生及腺瘤局部恶变时呈高表达,与组织的增生程度和息肉恶变的危险性之间具有相关关系,GAS高表达时COX-2表达增高,同时Ki-67表达亦增高。提示GAS、COX-2在结直肠腺瘤性息肉发生、发展及恶变过程中扮演重要的角色。

     

    Abstract: Objective: To investigate the relationship between gastrin and cyclooxygenase-2(COX-2) expression andproliferation, differentiation and malignant transformation of colorectal adenomas. Methods: The expression of gastrin,COX-2 and Ki-67 was detected by immunohistochemistry in 68 samples of colorectal adenoma, 10 samples of non-ade-noma and 15 samples of normal colonic mucosa. Those patients with inflammatory bowel disease, familial polyposis coli ora history of taking non-steroidal anti-inflammatory drugs (including low-dose aspirin) or glucocorticoid and proton pumpinhibitors were excluded. Results: The expression of gastrin and COX-2 was higher in adenoma tissues (P<0.01), especial-ly in villous adenoma, severe dysplasia and polyps with malignant transformation. Correlation analysis showed that gastrinand COX-2 expression levels were significantly related to pathological type and dysplasia grade of polyps (P<0.01). Fur-thermore, a positive correlation between COX-2 and gastrin expression (r=0.67, P<0.01) was found. The expression of Ki-67 was significantly higher in patients with expression of both gastrin and COX-2 than in patients without expression ofgastrin or COX-2 (P<0.01). Conclusion: Increased expression of gastrin and COX-2 is involved in the mechanisms ofgrowth and malignant transformation of adenoma, and it may play an important role in the progression of colorectal adeno-ma. Gastrin may induce COX-2 expression and co-stimulate cell proliferation during the growth and malignant transfor-mation of adenoma.

     

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