微卫星不稳定和错配修复基因异常在喉鳞状细胞癌中相关性研究(英文)

Microsatellite instability and abnormal mismatch repair in laryngeal squamous cell carcinoma

目的研究喉鳞状细胞癌中微卫星不稳定(microsatelliteinstability,MSI)发生的临床意义及其与错配修复基因(mismatchrepairgene,MMR)表达的相关性。方法50例喉鳞状细胞癌患者的石蜡切片选自北京同仁医院2002年至2003年的手术标本,利用显微切割-多聚酶链反应-单链长度多态性分析-银染的方法进行MSI的检测,统计MSI的发生率及其与临床资料的相关性,应用免疫组织化学观察MMR中hMLH1和hMSH2的表达。五个微卫星位点位于染色体1p,3p,5q,9p,17p上,分别临近BCAR3(breastcanceranti-estrogenresistance3),FHIT,APC,CDKN2A(p16),TP53等基因。结果在五个微卫星位点(D17S796,D3S3544,D5S656,D1S375,D9S162)提供统计信息的病例数分别是44,42,45,44和40例。MSI的发生率低于杂合性缺失(lossofheterozygosity,LOH)的发生率。MSI的发生率分别是:D17S796(TP53)20.5%(9/44),D3S3544(FHIT)14.3%(6/42),D5S65631.1%(14/45),D1S375(BCAR3)20.5%(9/44),D9S162(CDKN2A)15.0%(6/40)。MSI的发生与年龄、性别、吸烟史、肿瘤部位、肿瘤分化、TNM分期的关系没有统计学意义(P>0.05),但是与肿瘤复发的相关性具有统计学意义(P<0.01)。MSI的发生与MMR的表达存在相关性(P<0.01)。MMR阳性细胞和阴性细胞共存在同一张切片内是MMR免疫组织化学的特点。结论微卫星不稳定和错配修复基因异常可能参与部分喉鳞状细胞癌的发生,微卫星不稳定可能是喉鳞癌复发的特征性指标。

OBJECTIVE The aim of our study was to evaluate the significance of the frequency of microsatellite instability （MSI） and its relationship to mismatch repair gene （MMR） in laryngeal squamous cell carcinoma. METHODS We investigated the expression frequency and clinical significance of MSI and MMR in 50 laryngeal squamous cell carcinoma （LSCC） patients from Beijing Tongren Hospital. The status of MSI was evaluated using microdissection - polymerase chain reaction （PCR） - single strand length polymorphism （SSLP） - silver staining. Five markers on chromosomes lp, 3p, 5q, 9p, 17p, which were adjacent to BCAR3 （breast cancer anti-estrogen resistance 3）, FHIT, APC, CDKN2A （p16）, TP53 respectively, were used. Two of the six components of MMR - hMLH1 and hMSH2- were investigated by an immunohistochemical approach because of the high frequency of their downregulation in head and neck tumors. RESULTS The informative case number of the five markers （D17S796, D3S3544, D5S656, D1S375, D9S162） were 44, 42, 45, 44 and 40 respectively. The incidence of MSI was lower than the frequency of loss of heterozygosity （LOH）. The incidence of MSI on D17S796 （TP53） was 20.5% （9/44）,on D3S3544 （FHIT） was 14.3 % （6/42）, on D5S656 （APC） was 31.1% （14/45）, on D1S375 （BCAR3） was 20.5 % （9/44）, and on D9S162 （CDKN2A） was 15.0 % （6/40）. Though there was no relationship between MSI status and age, gender, smoke history, tumor location, tumor differentiation and T stage （P〉0.05）, there was a strong correlation between MSI and relapse condition （P〈0.01）. Also, MSI status correlated with MMR expression to some degree （P〈0.01）, but it was common for negative and positive staining of MMR to coexist on the same slide. CONCLUSION Microsatellite instability and abnormal mismatch repair may contribute to the carcinogenesis of a subset of laryngeal squamous cell carcinoma. Microsatellite instability may be a characteristic signal of tumor recurrence.