胃癌における癌抑制遺伝子P53とgenetic instability

抑癌基因P53与胃癌遗传不稳定性

• 批准号: 06770973
• 负责人: 大野 真司
• 金额: $ 0.58万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Encouragement of Young Scientists (A)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 无数据
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06770973/
• 关键词: 癌遺伝子; p53遺伝子; genetic instability; 胃癌; 増殖活性

癌抑制遺伝子p53の異常とgenetic instabilityの関連を明らかにする目的で、胃癌組織における異常p53の発現を検索し、さらにgenetic instabilityの指標としてのDNA ploidy pattern、および増殖活性との相関を検討した。(1)対象:1989年から1990年までに九州大学第二外科および関連施設にて切除された胃癌症例96例を対象とした。(2)方法:切除胃癌の先進部の凍結標本を用いて、免疫組織学的手法によりp53異常蛋白発現と増殖活性(Ki-67陽性細胞率)を、またFACScan flowcytometerによりDNA ploidy patternを検索した。(3)結果:対象96例のうち、52例(54%)にp53異常蛋白発現を認めた。p53異常蛋白陽性群52例のDNA Indexの平均値は1.3±0.28でAneuploid症例は36例(69%)であった。一方、p53異常蛋白陰性群44例のDNA Indexの平均値は1.19±0.26でAneuploid症例は20例(45%)であり、いずれも両群間に有意差を認めた(P<0.05)。増殖活性との相関をみると、p53異常蛋白陽性群のKi-67陽性細胞率は30.6±12%であり、陰性群の25.1±10.7%に比べ有意に高かった。(4)考察:p53異常を有するヒト体細胞癌では、genetic instabilityが増加し、DNA全体としてみた場合Aneuploid patternとしてgenetic instabilityをとらえることが可能と思われる。今回の我々の検討では、異常p53蛋白の発現が約半数に認められ、陽性群では陰性群に比べて、有意にAneuploid patternの割合が多く、高い増殖活性を示した。今後、癌の発生と進展課程におけるp53遺伝子の意義について検討し、さらに制癌剤感受性や治療効果との関連について研究を進める予定である。

To investigate the relationship between abnormal p53 and genetic instability in cancer suppressor gene, to detect abnormal p53 expression in gastric cancer tissue, to investigate the correlation between genetic instability and DNA ploidy pattern, and to investigate the relationship between genetic instability and reproductive activity. (1)Target: From 1989 to 1990, 96 cases of gastric cancer were resected by the Second Department of Surgery of Kyushu University. (2)Methods: To detect DNA ploidy pattern by FACScan cytometer, and to detect p53 abnormal protein expression and proliferation activity (Ki-67 positive cell rate) in frozen specimens of advanced gastric cancer. (3)Results: 96 cases were found abnormal p53 protein, 52 cases (54%) were found abnormal p53 protein. DNA Index of 52 cases with abnormal p53 protein group was 1.3±0.28, and 36 cases (69%) with Aneuploid syndrome. DNA Index of 44 cases with abnormal p53 protein negative group was 1.19±0.26, and that of 20 cases with Aneuploid syndrome (45%) was significantly different (P<0.05). The Ki-67 positive cell rate of p53 abnormal protein positive group was 30.6±12%, while that of p53 abnormal protein negative group was 25.1±10.7%. (4)To investigate the presence of p53 abnormalities in somatic cell carcinoma, genetic instability increased, DNA as a whole, Aneuploid pattern, genetic instability, and possible causes. In this study, we found that abnormal p53 protein expression was about half of the total, positive and negative groups were higher than those of the control group, and the Aneuploid pattern was higher than that of the control group, indicating that the abnormal p53 protein expression was higher than that of the control group. In the future, cancer development and progress courses will be conducted in the future. The significance of p53 gene will be discussed in the future. The sensitivity of cancer control agents and the effect of treatment will be discussed in the future.

项目成果

S.Ohno: "Clinicopathologic characteristics and outcome of adenocarcinoma of the human gastric cardia in comparison with carcinoma of other regions of the stomach" J.Am.Coll.Surg.(in press).

S.Ohno：“与胃其他区域的癌相比，人胃贲门腺癌的临床病理特征和结果”J.Am.Coll.Surg.（出版中）。