摘要
目的 探讨总结遗传性非息肉病性结直肠癌 (hereditarynonpolyposiscolorectalcancer,HNPCC)的临床和分子生物学特征 ,提高临床诊断和治疗水平。方法 分析总结温州地区 12个HNPCC家系临床病理特征。用显微切割、微卫星不稳定性分析、免疫组织化学、直接DNA测序法 ,检测HNPCC患者肿瘤组织微卫星不稳定性状态 ,错配修复基因hMHL1和hMSH2蛋白水平表达及hMHL1和hMSH2基因种系突变。结果 12个家系 32例患者中 ,患第 1癌的中位年龄 4 5 2岁 ;75 0 %的患者在 5 0岁以前发病 ;5 1 1%的肿瘤位于脾曲近侧结肠 ,34 4 %为多原发结直肠癌 ,5 3 1%为组织分化差的癌 ,6 8 8%为DukesA、B期。 12个家系中 6个家系伴有 7例肠外肿瘤患者 ;19例健在患者生存 1～ 2 8年 ,13例死亡患者平均生存期 6 4年。 9例患者肿瘤组织均表现高度微卫星不稳定性 ,其中 5例患者表现hMSH2或hMLH1蛋白失表达 (5 / 9) ;5个家系中 3个家系存在hMHL1或hMSH2突变 (3/ 5 ) ,其中有 2个新发现的突变。结论 HNPCC有特定的临床病理特征 ;检测错配修复基因hMHL1和hMSH2序列对HNPCC家系的成员具有指导价值 ;微卫星不稳定性和错配修复蛋白失表达是HNPCC的重要特征 。
Objective To study the clinicopathological and molecular genetic characteristics of hereditary nonpolyposis colorectal cancer (HNPCC), to enable the early diagnosis and to evaluate the treatment. Methods We analyzed 12 families of HNPCC from Wenzhou, Zhejiang province, China. Mismatch repair genes hMSH2 and hMLH1 expression and microsatellite instability of tumor tissue were studied using microdissection, microsatellite anlalysis, immunohistochemical staining and Gene Scan analysis. Direct DNA sequencing of hMSH2 and hMLH1 were performed subsequently. Results Altogether 32 patients with colorectal cancer were recognized in 12 HNPCC families, with the median age of 45 2 years (75 0% before the age of 50 years). The proximal tumors accounted for 51 1%, while multiple colorectal cancers accounted for 34 4%. Poor differentiation cancers occupied half of the patients (53 1%). And 68 8% of the patients had the tumor of Dukes A and B.Among 12 HNPCC families, 7 cases in 6 HNPCC families developed extracolonic cancer. 13 cases died during follow up of 1～23 years. The median survival time was 6 4 years. 19 alive cases followed up from 1 to 28 years All tumors (9/9) displayed microsatellite instability, with the half losing hMSH2 or hMLH1 expression. In the 5 genetic analyzed kindreds 3 possessed germline mutation. Two of three mutations have not been reported in the worldwide database previously. Conclusion HNPCC showed distinct clinicopathological characteristics. Microsatellite instability analysis and immunohistochemical staining might be the effective screening methods before direct DNA sequencing for the detection of mutation in mismatch repair genes. It is important to analyze the members of affected families.
出处
《中华外科杂志》
CAS
CSCD
北大核心
2004年第3期158-162,共5页
Chinese Journal of Surgery
基金
温州市医药卫生科学研究基金资助项目 ( 990 0 6)
关键词
遗传性非息肉病性结直肠癌
家系
分子遗传学
免疫组织化学
序列分析
突变
Colorectal neoplasms,hereditary nonpolyposis
Immunohistochemistry
Sequence analysis
Mutation
Microsatellite instability
