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

目的：研究p53、Rb和P16 3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、重度异型增生病灶的分别为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，重度病变中p53表达率与胃癌组相似，提示p53基因突变是胃癌发生过程中的早期事件。Rb蛋白在癌变组中缺失率较异型增生显著，可能是胃癌发生过程中的较晚事件。推测在p53基因突变的基础上加以Rb蛋白的缺失最终导致胃粘膜上皮癌变。p16蛋白的表达在胃癌发生过程的3个阶段病变中无显著的变化，可能不起要作用。不同类型（隐窝型、腺瘤型、再生型）异型增生间、癌旁或良性病变旁的异型增生间，不同分化程度的胃腺癌组间这3种抑癌基因蛋白表达状态基本相同。

The significance of the expression of tumor suppressor genes (p53

Aim：To study the expression of p53、Rb 、p16 in different stage ofdysplasia 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.