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Molecular pathological analysis on the precancerous lesions and early changes in the multistep carcinogenesis of human stomach

人胃癌多步癌变过程中癌前病变及早期变化的分子病理学分析

基本信息

批准号：
05670173
负责人：
ITO Hisao
金额：
$ 1.34万
依托单位：
Tottori University, Faculty of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

项目摘要

This study was couducted to examine gastric precancerous lesions molecular pathologically to clarify their significance on the development of gastric cancers.P53 protein positive cells were noted in intestinal metaplastic mucosa, but not in normal gastric mucasa. PCR-SSCP and fluorescence in situ hydridization (FISH) revealed point mutation of p53 genes (exon 5 and 8) in two of the five specimens with intestinal metaplasia, while loss of the genes was not confirmed. Apoptotic cells were demonstrated by both light microscopy and terminal deoxynucleotidy1 transferase-mediated DUTP-biotin nick end labeling (TUNEL). They distributed in a deeper portion of the metaplastic glands, near proliferative zone, the frequency being higher in incomplete type than in complete type. Metaplastic mucosa expressed c-ERBB2 and c-ERBB3 gene product variably, suggesting the role of their proliferation.Forty-five gastric tubular adenomas contained apoptotic cells variably, the frequency being significantly (p<0.05) higher in the adenomas showing high grade dysplasia than those with low grade dysplasia. Apoptosis were detected from 7.7 to 14.5% of all gastric cancer cells in 9 well differentiated carcinomas, and from 2.7 to 7.5% in 5 poorly differentiated carcinomas, the frequency being significantly (p<0.01) higher in the former than in the latter. No immunoreactivity for p53 protein was demonstrated in the tubular adenoma, in which no numerical aberration of chromosome 17 and p53 gene was noted. Immunoreactivity for c-ERBB2 and c-ERBB3 gene products was weak in the adenomas.These results indicated that p53 gene aberration occurred in gastric intestinal metaplasia. Precancerous lesion including metaplastic glands and tubular adenomas variably contained apoptotic cells which play a crucial roles not only in their morphogenesis, but also in the proliferation of the tumor cells.

本研究对胃癌前病变进行分子病理学检查，以明确其在胃癌发生发展中的意义。P53蛋白阳性细胞在肠化生黏膜中可见，而在正常胃粘液中未见阳性细胞。PCR-SSCP和荧光原位杂交(FISH)显示5例肠化生组织中有2例P53基因(外显子5和8)发生点突变，但未证实该基因缺失。光镜和末端脱氧核苷酸转移酶介导的dUTP-生物素缺口末端标记法(TUNEL)均可检测到凋亡细胞。分布于化生腺体较深部位，靠近增殖区，不完全型高于完全型。45例胃管状腺瘤中均有不同程度的凋亡细胞存在，高度不典型增生的腺瘤细胞凋亡率显著高于低度不典型增生的腺瘤(p&lt；0.05)。9例高分化癌的凋亡率为7.7%~14.5%，5例低分化癌的凋亡率为2.7%~7.5%，前者的凋亡率显著高于后者(P<0.01)。管状腺瘤未见P53蛋白阳性表达，未见17号染色体和P53基因数目异常。C-ERBB2和c-ERBB3基因产物在胃腺瘤中免疫反应较弱，提示胃肠化生中存在P53基因异常。癌前病变包括化生腺和管状腺瘤均含有不同程度的凋亡细胞，这些细胞不仅在其形态发生过程中起着至关重要的作用，而且在肿瘤细胞的增殖中也起着至关重要的作用。