Tissue microarray immunohistochemical expression analysis of mismatch repair (hMLH1 and hMSH2 genes) in endometrial carcinoma and atypical endometrial hyperplasia:: Relationship with microsatellite instability
Tissue microarray immunohistochemical expression analysis of mismatch repair (hMLH1 and hMSH2 genes) in endometrial carcinoma and atypical endometrial hyperplasia:: Relationship with microsatellite instability
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DOI：
10.1097/01.mp.0000095646.70007.6a
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发表时间：
2003-11-01
期刊：
影响因子：
7.5
通讯作者：
Palacios, J
中科院分区：
文献类型：
--
作者：
Hardisson, D;Moreno-Bueno, G;Palacios, J
错配修复基因(hMLH1和hMSH2)的改变在散发性子宫内膜癌微卫星不稳定性的发生中起重要作用。组织微阵列技术允许在DNA、RNA和蛋白质水平上对肿瘤样本进行分子图谱分析。应用免疫组织化学方法检测了10例非典型子宫内膜增生症、58例子宫内膜样癌和27例非子宫内膜样癌组织中hMLH1和hMSH2的表达。结果与BAT-25和BAT-26评估的微卫星不稳定状态相关。总体而言，29.4%的病变表现出微卫星不稳定。HMLH1和hMSH2蛋白表达缺失率分别为22.3%和6.5%。免疫组织化学结果显示，在微卫星不稳定性阳性的子宫内膜病变中，hMLH1和hMSH2的蛋白表达缺失率分别为16.6%和16.6%。综上所述，24例微卫星不稳定性阳性病例中有18例hMLH1或hMSH2蛋白表达缺失(敏感性为75%)。免疫组织化学检测hMLH1和hMSH2与BAT-25和BAT-26评价微卫星不稳定状态具有高度一致性(kappa值为0.7)。在57例微卫星不稳定性阴性的病例中，53例两种蛋白均正常表达(93%特异性)。HMLH1表达缺失对微卫星不稳定阳性状态的预测价值为82%。这两种蛋白的正常表达对预测微卫星不稳定状态的预测值为90%。这些结果与以前在整个组织切片中报道的结果一致。因此，组织芯片上hMLH1和hMSH2表达的免疫组织化学分析为筛选微卫星不稳定性肿瘤提供了准确的技术手段。组织微阵列是在连续的组织微阵列切片中比较不同诊断或预测标记物彼此的理想方法。
Alterations in the mismatch repair genes (hMLH1 and hMSH2) play an important role in the development of microsatellite instability in sporadic endometrial cancer. Tissue microarray technology allows molecular profiling of tumor samples at the DNA, RNA, and protein levels. We analyzed hMLH1 and hMSH2 expression by immunohistochemistry in a group of atypical endometrial hyperplasias (n = 10), endometrioid endometrial carcinomas (n = 58), and nonendometrioid endometrial carcinomas (n = 27) on tissue micro,array. The results were correlated with microsatellite instability status as evaluated by BAT-25 and BAT-26. Overall, 29.4% of lesions showed microsatellite instability. Loss of nuclear hMLH1 and hMSH2 protein expression was seen in 22.3% and 6.5% of cases, respectively. Immunohistochemistry for hMLH1 and hMSH2 showed lack of protein expression in 64% and 16.6% of microsatellite instability-positive endometrial lesions, respectively. Taken together, hMLH1 or hMSH2 protein expression was absent in 18 of 24 microsatellite instability-positive cases (75% sensitivity). A high level of concordance was found between immunohistochemistry for hMLH1 and hMSH2 and microsatellite instability status evaluated by BAT-25 and BAT-26 (kappa value of 0.7). Of the 57 cases found to be microsatellite instability negative, 53 showed normal expression of both proteins (93% specificity). The observed predictive value of absence of expression of hMLH1 for predicting microsatellite instability-positive status was 82%. The predictive value of normal expression of both proteins for predicting microsatellite instability-negative status was 90%. These results are consistent with those previously reported in whole tissue sections. Therefore, immunohistochemical analysis of hMLH1 and hMSH2 expression on tissue microarray provides an accurate technique for screening for tumors with microsatellite instability. Tissue microarrays represent an ideal approach for comparing different diagnostic or predictive markers with one another in consecutive tissue microarray sections.