CAJ | 학술논문

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蛋白在癌变组中的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，可能不起主要作用.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. 目的：研究p53、Rb和p163箇抑癌基因在正常胃粘膜→異型增生粘膜→胃癌髮展過程中的錶達狀態及相互關繫.方法：收集胃手術及胃鏡活檢標本共60例，鏡下觀察胃粘膜併選取不同部位、不同程度的異型增生腺體病竈共99處。應用免疫組化檢測p53、Rb、p16蛋白在99箇異型增生病竈、35例胃腺癌和32例正常胃粘膜中的錶達情況.應用聚閤酶鏈反應單鏈構象多態性分析技術（PCR-SSCP）對35例胃腺癌進行p16基因點突變檢測.結果：p53暘性率在輕、中、重度異型增生病竈中分彆為7.5%、35.1%、59.1%，胃癌組為68.6%，正常對照組中無錶達.Rb蛋白暘性率在輕、中、重度異型增生病竈中分彆為80.0％、89.3％、81.8％，胃癌組為57.1％，正常對照組為90.6％.p16蛋白在正常胃粘膜、異型增生粘膜和胃癌中普遍錶達，3組間暘性率比較無顯著性差異.p16基因PCR-SSCP分析示隻有1例低分化腺癌齣現異常單鏈泳動帶.不同類型（隱窩型、腺瘤型、再生型）異型增生病竈組間、位于癌徬和良性病變徬的異型增生病竈組間p53、Rb和p16蛋白的暘性率無顯著性差異.高－中分化、低分化、未分化胃癌組間p53、Rb和p16蛋白的暘性率無顯著性差異.結論：突變型p53蛋白的積聚在胃粘膜異型增生階段已經開始，隨著異型增生程度的加重逐漸增加，重度病變中p53錶達率與胃癌組相似，提示p53基因突變是胃癌髮生過程中的早期事件.Rb蛋白在癌變組中的缺失率較異型增生顯著，可能是胃癌髮生過程中的較晚事件.推測在p53基因突變的基礎上加以Rb蛋白的缺失最終導緻胃粘膜上皮癌變.p16蛋白的錶達在胃癌髮生過程的3箇階段病變中無顯著的變化，可能不起主要作用.不同類型（隱窩型、腺瘤型、再生型）異型增生間、癌徬或良性病變徬的異型增生間，不同分化程度的胃腺癌組間這3種抑癌基因蛋白錶達狀態基本相同.
목적：연구p53、Rb화p163개억암기인재정상위점막→이형증생점막→위암발전과정중적표체상태급상호관계.방법：수집위수술급위경활검표본공60례，경하관찰위점막병선취불동부위、불동정도적이형증생선체병조공99처。응용면역조화검측p53、Rb、p16단백재99개이형증생병조、35례위선암화32례정상위점막중적표체정황.응용취합매련반응단련구상다태성분석기술（PCR-SSCP）대35례위선암진행p16기인점돌변검측.결과：p53양성솔재경、중、중도이형증생병조중분별위7.5%、35.1%、59.1%，위암조위68.6%，정상대조조중무표체.Rb단백양성솔재경、중、중도이형증생병조중분별위80.0％、89.3％、81.8％，위암조위57.1％，정상대조조위90.6％.p16단백재정상위점막、이형증생점막화위암중보편표체，3조간양성솔비교무현저성차이.p16기인PCR-SSCP분석시지유1례저분화선암출현이상단련영동대.불동류형（은와형、선류형、재생형）이형증생병조조간、위우암방화량성병변방적이형증생병조조간p53、Rb화p16단백적양성솔무현저성차이.고－중분화、저분화、미분화위암조간p53、Rb화p16단백적양성솔무현저성차이.결론：돌변형p53단백적적취재위점막이형증생계단이경개시，수착이형증생정도적가중축점증가，중도병변중p53표체솔여위암조상사，제시p53기인돌변시위암발생과정중적조기사건.Rb단백재암변조중적결실솔교이형증생현저，가능시위암발생과정중적교만사건.추측재p53기인돌변적기출상가이Rb단백적결실최종도치위점막상피암변.p16단백적표체재위암발생과정적3개계단병변중무현저적변화，가능불기주요작용.불동류형（은와형、선류형、재생형）이형증생간、암방혹량성병변방적이형증생간，불동분화정도적위선암조간저3충억암기인단백표체상태기본상동.
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.