广东籍中老年人结直肠癌分子遗传学的致癌途径

Molecular genetic pathway of middle-aged and senile patients with colorectal carcinomas in Guangdong district

目的 探讨中国广东地区中老年人 (年龄 >5 0岁 )结直肠癌 (CRC)的分子致癌途径。方法 应用流式细胞学和免疫组化方法检测 6 0例中老年人CRCs的DNA倍性及p5 3、hMSH2 和hMLH1蛋白表达 ,结合临床病理学资料 ,分析它们之间的相关性。结果 在 6 0例广东籍中老年大肠癌患者中 ,有 4 3例 (71 7% )为非整倍体DNA的含量 ,39例 (6 5 0 % )出现 p5 3蛋白过度表达 ,2例 (3 3% )丢失了hMSH2 或hMLH1蛋白。这组CRC的DNA倍性与p5 3蛋白表达有关 (χ2 =5 6 83,P =0 0 17) ,4 3例非整倍体DNA含量的CRC中 ,有 33例 (76 7% )呈 p5 3蛋白过度表达。丢失了hMSH2 或hMLH1蛋白的 2例CRC ,全部为二倍体的DNA含量 ,均呈 p5 3蛋白的正常表达 ,另外有 15例 (2 5 % )肿瘤既未出现非整倍体DNA含量 ,又未丢失hMSH2 或hMLH1蛋白 ,其中多数 (10 / 15 )表达正常的p5 3蛋白。结论 在中国广东地区中老年人CRC中 ,hMSH2 或hMLH1蛋白的丢失率低 ,多数 (71 7% )

Purpose To investigate the molecular genetic pathway of middle aged and senile (age>50) patients with colorectal carcinomas (CRC) in Guangdong, China. Methods Flow cytometry and immunohistochemistry were used to detect the status of DNA ploidy and expression of p53, hMSH 2 and hMLH 1 in 60 cases of middle aged and senile CRC from Guangdong province. The correlation between these molecular features was analyzed with their clinic pathologic data. Results Of the 60 middle aged and senile CRC studied, 43 cases of CRC (71 7%) had aneuploid DNA content, 39 cases (65 0%) showed over expression of p53, 2 cases (16 9%) lost mismatch repair protein, hMSH 2 or hMLH 1. In this group of CRC, the expression of p53 had a significant correlation with tumor's DNA ploidy (χ 2=5 683, P =0 017), where over expression of p53 were observed in most cases (33/43) of DNA aneuploid CRC. The two CRC with loss of hMSH 2 or hMLH 1 protein were all diploid DNA content and showed normal expression of p53. In addition, there were 15 cases (25%) of CRCs showing no loss of either MMR proteins and having a diploid or near diploid DNA content, and majority of them (10/15) expressed p53 protein normally. Conclusions In Guangdong, the incidence of loss of hMSH 2 or hMLH 1 protein in middle aged and senile CRC was low and majority (71 7%) of CRC were developed via the chromosomal instability pathway.