胃癌增生凋亡与调节基因的表达

Proliferation/apoptosis and expression of P53 and Bcl-2 in gastric carcinoma

目的:研究胃癌、癌前病变(异型增生、肠化生、萎缩性胃炎)细胞增生凋亡及其调节基因表达,探讨胃癌多阶段发生.方法:采用病理组织学对24例胃癌、14例癌旁异型增生、24例远离癌灶的慢性胃炎和32例肠化生胃黏膜进行分类、分期、分度,Ki67,P53及Bcl-2免疫组化染色,TUNEL(ISEL)技术检测细胞凋亡.计算各种病变的Ki67增生指数和凋亡指数、凋亡增生比、凋亡强度,和P53,Bcl-2的阳性例数和百分比.结果:胃癌、异型增生、肠化生和萎缩性胃炎的增生指数分别是12.4±6.8%,6.4±4.2%,6.6±3.4%和3.8±2.9%,浅表性胃炎与各组均有非常显著差异(P<0.01).凋亡指数分别是2.4±1.4%,2.6±1.6%、3.1±1.2%和3.8±2.0%;凋亡强度分别是0.3,0.6,079和1.3.以萎缩性胃炎最高,与其他各组间均有非常显著差异(P<0.01),中、重度异型增生和胃癌相互间无显著性差异(P>0.05).重度异型增生和早期胃癌的凋亡强度是浅表性胃炎的1/3,进展期胃癌仅为其1/5.P53蛋白在胃癌、异型增生、肠化生、萎缩性胃炎分别是25.0%,14.3%,3.1%和0%.Bcl-2的表达分别是58.3%,42.8%,9.4%和7.1%,在胃癌和异型增生P53蛋白和Bcl-2表达相互间存在显著相关性(P<0.05).结论:P53和Bcl-2基因不仅在胃癌表达,在癌前病变异型增生、肠化生也有部分表达,萎缩性胃炎不具有上述特点.

AIM:To study proliferation and apoptosis in gastric carcinoma (GC) and precancerous lesions and expression of their regu- lating genes. METHODS:Total 24 cases of GC, 14 dysplasia (DP), 24 chronic gastritis (10 superfical gastritis, SG, 14 atrophic gastritis, AG) and 32 intestinal metaplasia (IM) were studied by histopathological, immunohistochemical techniques with Ki67, P53 and Bcl-2 antibodies, and by TUNEL for apoptosis. Proliferation index (PI), apoptosis index (AI), apoptosis/ proliferation ratio, apoptosis degree and positive percent of P53 and Bcl-2 were counted. RESULTS:The PI of GC, DP, IM, AG were 12.4±6.8 %, 6.4±4.2 %, 6.6±3.4 %, 3.8±2.9 % respectively. There was a significant difference between SG and GC, DP, IM, and AG (P <0.01). The AI of GC, DP, IM, and AG was 2.4±1.4 %, 2.6±1.6 %, 3.1±1.2 % and 3.8±2.0 % respectively. The apoptosis degree of AG was the highest, and significantly higher than that of GC, DP, and IM (P <0.01). There was no significantly different among GC, moderate and severe DP (P >0.05). Mucosa in AG showed excessive apoptosis, however the apoptosis degree in severe DP and early gastric carcinoma was about 1/3 of SG, and in advanced GC was its 1/5. The positive percentages of P53 in GC, DP, IM and AG were 25.0 %, 14.3 %, 3.1 % and 0 % respectively. The positive rate of Bcl-2 was 58.3 %, 42.8 %, 9.4 % and 7.1 % respectively. There was a significant correlation beween P53 and Bcl-2. CONCLUSION:Mutated P53 gene and Bcl-2 apoptosis regu- lating gene not only express in GC, also partly express in DP, IM, and in those precancerous lesions in which gastric carcinogenesis may have been initialized. The imbalancebetween proliferation and apoptosis is manifestation of the gene mutations on the cytodynamics. The DP and IM may be the different stages in gastric carcinogenesis.