p53、Rb、p16抑癌基因在胃粘膜上皮异型增生病变中表达的意义

The significance of the expression of tumor suppressor genes (p53、Rb、p16) in gastric mucosa epithelial dysplasis

目的 :研究p53、Rb和p163个抑癌基因在正常胃粘膜→异型增生粘膜→胃癌发展过程中的表达状态及相互关系 方法 :收集胃手术及胃镜活检标本共 60例 ,镜下观察胃粘膜并选取不同部位、不同程度的异型增生腺体病灶共 99处。应用免疫组化检测p53、Rb、p16蛋白在 99个异型增生病灶、35例胃腺癌和 32例正常胃粘膜中的表达情况 应用聚合酶链反应单链构象多态性分析技术 (PCR -SSCP)对 35例胃腺癌进行p16基因点突变检测 结果 :p53阳性率在轻、中、重度异型增生病灶中分别为 7.5%、35.1%、59.1% ,胃癌组为 68.6% ,正常对照组中无表达 Rb蛋白阳性率在轻、中、重度异型增生病灶中分别为 80 .0 %、89.3%、81.8% ,胃癌组为 57.1% ,正常对照组为90 6% .p16蛋白在正常胃粘膜、异型增生粘膜和胃癌中普遍表达 ,3组间阳性率比较无显著性差异 p16基因PCR -SSCP分析示只有 1例低分化腺癌出现异常单链泳动带 不同类型 (隐窝型、腺瘤型、再生型 )异型增生病灶组间、位于癌旁和良性病变旁的异型增生病灶组间p53、Rb和p16蛋白的阳性率无显著性差异 高 -中分化、低分化、未分化胃癌组间p53、Rb和p16蛋白的阳性率无显著性差异 结论 :突变型p53蛋白的积聚在胃粘膜异型增生阶段已经开始 ,随着异型增生程度的加重逐渐增加 ,重?

Aim:To study the expression of p53、Rb 、p16 in different stage of dysplasia from normal gastric mucosa epithelial to carcinoma. Methods: The proteins of p53、Rb 、p16 were detected by immunohistochemistery in 99 dysplasia foci of 60 cases of gastric mucosa and 35 cases of gastric carcinoma. The p16 gene's point mutation was detected by PCR-SSCP in 35 cases of gastric carcinoma. Results: The positive rate of p53 was 29.3%in 99 gastric dysplasia foci, 7.5% in light grade dysplasia, 35.1% in medium grade dysplasia, 59.1% in severe grade dysplasia, 68.6% in gastric carcinoma and negative in normal gastric mucosa. The positive rate of pRb was 83.8% in 99 dysplasia foci, 80.0% in light grade dysplasia, 89.2% in medium grade dysplasia, 81.8% in severe grade dysplasia, 57.1% in gastric carcinoma and 90.6% in normal gastric mucosa. p16 was commonly expression in normal gastric tissue, dysplasia and carcinoma. The point mutation of p16 gene was detected only in one case of poorly differentated adenocarcinoma. The expression of p53, pRb and p16 had no statistical difference between adenomatous, cryptal and regeneration dysplasia, also between cancer-adjacent dysplasia and benign lesion-adjacent dysplasis. Conclusion: The accumulation of p53 may happen in the early stage of gastric carcinogenesis. The deletion fo pRb was often found in cancerous stage but not in the normal tissue and dysplasia. The carcinogenesis of gastric carcinoma is possibly based on the mutation of p53 gene while the deletion of Rb gene. The effect of p16 gene may be not important in carciongenesiss of gastric carcinoma. [