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目的探讨多种基因改变在癌前病变及胃癌组织中的作用,方法应用 PCR-RFLP,PCR-SSCP,RT-PCR 及免疫组化技术同时对60例肠化生,30例异型增生及52例胃癌组织中抑癌基因 APC,MCC,DCC,YNZ22,p53及癌基因 Ki-ras,Bcl-2多种变异形式进行检测。结果随着肠化生粘膜向异型增生、胃癌的发展,多种基因改变的频率逐步升高,胃癌组织中 APC,DCC,YNZ22,p53,Bcl-2的改变频率分别为57.7%(30/52),43.1%(22/51),51.6%(16/31),67.3%(35/52),68.6%(35/51)显著高于肠化生上述基因的改变(APC 33.3%,DCC4.3%,YNZ22 19.4%,p5326.7%,Bcl-2 33.3%)(P<0.05,0.01),异型增生组织中DCC 基因改变为12.5%(3/24),也显著低于胃癌组织中的改变.Ⅲ型肠化中 APC 及 bcl-2基因蛋白表达率分别为61.1%,55.6%,p53突变及蛋白表达率为57.1%,27.8%,显著高于Ⅰ,Ⅱ型肠化中 APC,Bcl-2蛋白表达率(6.3%,23.8%)(P<0.01,O.05)及 p53突变及蛋白表达率(18.2%,2.4%)(P<0.05).肠型胃癌 APC,p53,Ki-ras 突变率分别为52.9%;82.4%;29.4%,显著高于胃型胃癌各基因的突变(APC 18.2%;p53 45.8%;Ki-ras 3.0%)(P<0.05).肠型胃癌 APC,Ki-ras,bcl-2基因的蛋白表达率分别为76.5%;41.2%;93.8%,胃型胃癌分别为30.3%;3.0%;54.5%,两型相比差别显著(P<0.01,0.05).APC,p53及 Bcl-2基因可能是肠化生癌变及肠型胃癌的热点基因,肠化生及异型增生阶段即可检测到基因改变的累积现象,但以胃癌组织中最显著。结论多种基因改变的累积与胃癌的发生及演进密切相关,不同类型肠化生分子改变机制不同,APC,p53及 Bcl-2基因有可能成为肠型胃癌早期诊断的分子标志。
Objective To investigate the role of multiple gene alterations in precancerous lesions and gastric cancer. Methods Sixty cases of intestinal metaplasia, 30 dysplasia and 52 cases of dysplasia were studied by PCR-RFLP, PCR-SSCP, RT-PCR and immunohistochemistry Gastric cancer tissue suppressor gene APC, MCC, DCC, YNZ22, p53 and oncogene Ki-ras, Bcl-2 variants were detected. Results The frequencies of APC, DCC, YNZ22, p53 and Bcl-2 in gastric cancer were 57.7% (30/52) with the progression of intestinal metaplasia to dysplasia and gastric cancer. ), 43.1% (22/51), 51.6% (16/31), 67.3% (35/52) and 68.6% (35/51), respectively, which were significantly higher than those in intestinal metaplasia (APC 33.3%, DCC4). 3%, YNZ22 19.4%, p5326.7%, Bcl-2 33.3%) (P <0.05,0.01), DCC gene mutation in dysplasia tissues was 12.5% (3/24), which was also significantly lower than that in gastric cancer tissues .The protein expression rates of APC and bcl-2 in type Ⅲ intestinal metaplasia were 61.1% and 55.6% respectively, the mutation rate of p53 and the protein expression rate were 57.1% and 27.8%, which were significantly higher than those of type Ⅰ and Ⅱ intestinal metaplasia (P <0.01, O.05), p53 mutation and protein expression (18.2%, 2.4%) (P <0.05) .The expression of APC, p53, Ki- ras mutation rates were 52.9%, 82.4% and 29.4%, respectively, which were significantly higher than those in gastric gastric cancer (APC 18.2%, p53 45.8% and Ki-ras 3.0% The protein expression rates of Ki-ras and bcl-2 were 76.5%, 41.2% and 93.8%, respectively. Gastric gastric cancer was 30.3%, 3.0% and 54.5% respectively, with significant difference between the two groups (P <0.01, 0.05) .APC, p53 and Bcl-2 genes May be intestinal metaplasia and intestinal gastric cancer hotspot genes, intestinal metaplasia and dysplasia stage can detect the accumulation of genetic changes, but the most significant in gastric cancer. Conclusions The accumulation of multiple gene alterations is closely related to the occurrence and evolution of gastric cancer. The mechanisms of the different types of intestinal metaplasia are different. APC, p53 and Bcl-2 genes may be the molecular markers for the early diagnosis of intestinal-type gastric cancer.