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目的探讨与年轻人结直肠癌(CRC)早期诊断和临床分期密切相关的分子标记。方法运用免疫组织化学和流式细胞学方法对63例年轻结直肠癌和对应的16例腺瘤组织中β-连接素(β-catenin)、hMSH2、hMLH1和P53蛋白表达和DNA倍性进行检测,结合肿瘤的Dukes分期,分析它们之间的差异与相关性。结果在63例年轻CRC中,肿瘤组织的DNA倍性与患者的Dukes分期有显著的相关性(P<0.05),非整倍体DNA含量的肿瘤,80.8%发生在DukesC或D期的CRC。P53蛋白的过度表达(76.0%)也倾向于浸润晚期的肿瘤;而hMSH2或hMLH1蛋白丢失的肿瘤70.0%是浸润早期的CRC。在16例配对的年轻结直肠腺癌和腺瘤组织中,β-catenin和DNA错配修复(MMR)蛋白表达间差异无显著性意义(P>0.05),8例β-catenin核浆聚集的CRC中,其对应的腺瘤有5例同时出现β-catenin的核浆聚集;丢失了hMSH2或hMLH1蛋白的3例CRC,其对应的3例腺瘤均丢失相应MMR蛋白。结论β-catenin和MMR蛋白hMSH2,hMLH1可以作为年轻CRC早期诊断中较为理想的分子标记;而肿瘤的DNA倍性和P53蛋白表达是患者临床分期中有用的参考指标。
Objective To investigate the molecular markers closely related to the early diagnosis and clinical stage of colorectal cancer (CRC) in young people. Methods The expression of β-catenin, hMSH2, hMLH1 and P53 protein and DNA ploidy in 63 cases of young colorectal cancer and 16 corresponding adenomas were detected by immunohistochemistry and flow cytometry , Combined with the Dukes stage of the tumor, analyze the differences and correlations between them. Results In 63 young CRC patients, the DNA ploidy of tumor tissue was significantly correlated with Dukes stage (P <0.05). Aneuploid DNA content of tumor was 80.8% in DukesC or D CRC. Overexpression of P53 protein (76.0%) also tended to infiltrate late stage tumors; whereas 70.0% of hMSH2 or hMLH1 lost tumors were early-infiltrated CRC. There were no significant differences in the expression of β-catenin and DNA mismatch repair (MMR) among 16 paired colorectal adenocarcinomas and adenomas (P> 0.05), and 8 cases of β-catenin nuclear aggregates In the CRC, 5 corresponding adenomas showed nuclear plasma accumulation of β-catenin. Three CRC patients lost the hMSH2 or hMLH1 protein, and all corresponding 3 adenomas lost the corresponding MMR proteins. Conclusion β-catenin and hMSH2 and hMLH1 can be regarded as ideal molecular markers for early diagnosis of young CRC. DNA ploidy and P53 protein expression are useful reference points in clinical staging of patients.