摘要目的 通过对子宫内膜黏液性上皮病变中的KRAS突变情况进行分析,探讨KRAS突变与子宫内膜黏液癌的相关性.方法 收集2015年7月至2017年10月首都医科大学附属北京妇产医院病理科诊断的子宫内膜黏液性上皮病变43例,不典型性子宫内膜增生症10例,子宫内膜样癌12例.从中性甲醛固定石蜡包埋组织中提取基因组DNA,聚合酶链反应(PCR)扩增KRAS第2、3号外显子,并进行毛细管电泳分析突变情况.应用Fisher确切概率法对各组中KRAS突变差异情况进行比较.结果 43例子宫内膜黏液性上皮病变患者年龄33～77岁,平均年龄(55.12±9.34)岁,中位年龄55岁.8例具有黏液分化的不伴细胞不典型性的子宫内膜增生症均未检出KRAS突变.不典型性子宫内膜增生症、子宫内膜样癌、不典型性子宫内膜增生症伴黏液分化、子宫内膜样癌伴黏液分化与黏液癌中存在KRAS突变,检出比例分别为1/10、1/12、4/11、6/15和8/9.黏液癌与子宫内膜样癌组(P<0.01)、子宫内膜样癌伴黏液分化组(P<0.05)相比,KRAS突变分布差异具有统计学意义.结论 不典型性子宫内膜增生症伴黏液分化、子宫内膜样癌伴黏液分化和黏液癌中存在KRAS高频突变,提示KRAS突变激活与子宫内膜黏液癌的发病机制密切相关.

abstractsObjective To investigate the frequency of KRAS mutation in mucinous epithelial lesions of the endometrium, and analyze the correlation between KRAS mutation and the clinicopathologic features. Methods The cohort included forty-three cases of mucinous epithelial lesions of the endometrium selected from July 2015 to October 2017 from Beijing Obstetrics and Gynecology Hospital, and 22 control cases. Genomic DNA was extracted from formalin-fixed paraffin-embedded tissue sections. Polymerase chain reaction amplification for KRAS exons 2 and 3 was performed, followed by sequencing using capillary electrophoresis. The Fisher exact test was used to compare the prevalence of KRAS mutation among the different groups. Results The patients′age ranged from 33 to 77 years [ mean ( 55. 12 ± 9. 34) years, median 55 years] . None of the eight cases of endometrial hyperplasia with mucinous differentiation without atypia showed KRAS mutation. The frequency of KRAS mutations was 1/10 in endometrial atypical hyperplasia, 1/12 in endometrioid carcinoma, 4/11 in endometrial atypical hyperplasia with mucinous differentiation ( EAHMD) , 6/15 in endometrioid carcinoma with mucinous differentiation ( ECMD) and 8/9 in mucinous carcinoma ( MC) , respectively. The differences were statistically significant between MC versus EC ( P<0. 01) and MC versus ECMD ( P<0. 05) . Conclusion The high frequency of KRAS mutation in&nbsp;EAHMD, ECMD and MC indicates that KRAS mutational activation is implicated in the pathogenesis of endometrial mucinous carcinoma.