1889例结直肠癌MSI、K-ras、N-ras和B-raf基因状态以及临床病理特征分析

Association of microsatellite instability,K-ras,N-ras and B-raf gene status with clinicopathologic features in 1889 patients with colorectal cancer

目的通过对1889例结直肠癌微卫星不稳定(MSI)、K-ras、N-ras和B-raf基因检测,分析其基因状态与临床病理特征之间的关联性。方法收集东部战区总医院病理科结直肠癌患者手术切除大标本共计1889例,通过PCR荧光法联合毛细管电泳法对1889例结直肠癌进行MSI、K-ras、N-ras和B-raf检测,分析其基因状态与临床病理特征之间的关系,以及MSI与K-ras、N-ras和B-raf之间的关联性分析,并且对MSI自身位点的相关性分析。结果1889例结直肠癌患者中,微卫星高度不稳定(MSI-H)更易发生于右侧结肠(16.4%)、黏液腺癌(14.9%)、分化程度较低(18.7%)、年龄偏低(8.3%)、淋巴结未转移(9.1%)以及B-raf突变(5.2%)的患者中,K-ras突变更易发生于右侧结肠(50.7%)、黏液腺癌(50.7%)、分化程度较高(52.1%)、微卫星低度不稳定或稳定型(42.2%)的患者中,而B-raf突变更易发生在MSI-H(6.9%)的患者中,而N-ras基因则与临床病特征关联性不强。结论结直肠癌患者的MSI、K-ras和B-raf基因状态与临床病理特征存在着高度的关联性,因此通过分析其基因状态与临床病理特征之间的关系可以为临床靶向治疗以及预后提供更加可靠的依据。

Objective To screen for mutations in microsatellite instability(MSI),K-ras,N-ras and B-raf genes in Chinese patients with colorectal cancer(CRC)and to explore their correlations with certain clinicopathological parameters.Methods We tested mutations in the MSI,K-ras,N-ras and B-raf genes using reverse transcriptase-polymerase chain reaction(RT-PCR)and capillary electrophoresis in a large cohort of 1,889 Chinese CRC patients who underwent surgical resection at the Department of Pathology,Nanjing Jinling Hospital.Results MSI-H status in CRC were closely associated with right-sided tumors(16.4%),histological type(14.9%),poorer differentiation(18.7%),younger age(8.3%),lymph node metastasis(9.1%)and B-raf mutation(5.2%).While mutant K-ras was closely associated with right-sided tumors(50.7%),histological type(50.7%),higher differentiation(52.1%)and MSI-L or MSS status(42.2%).B-raf mutation were significantly more prevalent in tumors with MSI-H status(6.9%),but N-ras has no strong correlations with certain clinicopathological parameters.Conclusion Further studies investigating the relationship between MSI/K-ras/N-ras/B-raf gene status and clinicopathological parameters can help in the development of treatment strategies for patients with CRC.