Molecular pathological analysis on the precancerous lesions and early changes in the multistep carcinogenesis of human stomach
| Project/Area Number |
05670173
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Human pathology
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| Research Institution | Tottori University, Faculty of Medicine |
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Principal Investigator |
ITO Hisao Department of Pathology, Tottori University, Faculty of Medicine, Professor, 医学部, 教授 (60127610)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1994: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1993: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Human gastric cancer / Precancerous lesion / Molecular pathology / Chromosome aneuploidy / FISH / Apoptosis / Oncogene products / P53 gene / アポートシス |
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| Research Abstract |
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.
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Report
(3 results)
Research Products
(16 results)
