Kwasniewska Anna, Postawski Krzysztof, Gozdzicka-Józefiak Anna, Zdunek Malgorzata, Korobowicz Elzbieta, Miturski Roman
Clinic I of Obstetrics and Gynecology, Skubiszewski University School of Medicine, ul. Staszica, 20-081 Lublin, Poland.
Int J Mol Med. 2005 Jun;15(6):955-61.
The immunohistochemical (IHC) detection of MMR proteins is an accurate and rapid method to predict the presence of defective DNA MMR genes. MMR protein expression could also serve as a prognostic indicator of human cancers. The results of many studies demonstrate the usefulness of IHC tests with monoclonal antibodies MSH2 and MLH1 in screening the microsatellite sequence instability within both spontaneous and hereditary malignant neoplasms. The aim of our study was to perform an IHC estimation of the hMLH1 and hMSH2 expression in a subset of vulvar carcinomas according to HPV 16/18 status. The level of MMR proteins was further analyzed in relation to histoclinical features of the disease in either HPV-positive or -negative cancers. We identified archival diagnostic phase tissue specimens from 46 cases of vulvar cancer. From the same paraffin blocks containing material from the margin of surgical section during vulvectomy, normal epithelial tissue fragments were collected and designated as the control group. The characteristic of the lesion was examined in comparison with the presence of HPV DNA. Identification of the HPV 16/18 types was performed using PCR. IgG1 monoclonal antibodies detecting those epitopes characteristic for hMLH1 and hMSH2 were used in the study. In the analyzed cases of vulvar cancer, we have observed increased expression of proteins of both hMSH2 and hMLH1 genes compared to the control group. A comparison of the hMLH1 and hMSH2 protein expression levels showed that hMSH2 expression was higher than that of hMLH1 in the case of vulvar carcinomas. The performed analysis of correlation between individual parameters did not reveal statistically significant relationship with both the gradient and status of HPV 16/18. hMSH2 and hMLH1 were definitely interrelated.
错配修复(MMR)蛋白的免疫组织化学(IHC)检测是预测DNA错配修复基因缺陷存在的一种准确且快速的方法。MMR蛋白表达也可作为人类癌症的预后指标。许多研究结果表明,使用单克隆抗体MSH2和MLH1进行的IHC检测在筛查自发性和遗传性恶性肿瘤中的微卫星序列不稳定性方面具有实用性。我们研究的目的是根据HPV 16/18状态,对一部分外阴癌中的hMLH1和hMSH2表达进行IHC评估。在HPV阳性或阴性癌症中,进一步分析MMR蛋白水平与疾病组织临床特征的关系。我们从46例外阴癌病例中鉴定出存档的诊断阶段组织标本。从包含外阴切除术中手术切缘材料的同一石蜡块中收集正常上皮组织碎片,并指定为对照组。将病变特征与HPV DNA的存在情况进行比较检查。使用PCR鉴定HPV 16/18类型。本研究使用检测hMLH1和hMSH2特征性表位的IgG1单克隆抗体。在分析的外阴癌病例中,我们观察到与对照组相比,hMSH2和hMLH1基因的蛋白表达均增加。hMLH1和hMSH2蛋白表达水平的比较表明,在外阴癌病例中,hMSH2表达高于hMLH1。对各个参数之间相关性的分析未发现与HPV 16/18的梯度和状态存在统计学上的显著关系。hMSH2和hMLH1肯定相互关联。