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首页> 外文期刊>Pathobiology: journal of immunopathology, molecular and cellular biology >Mismatch repair proteins hMLH1 and hMSH2 are differently expressed in the three main subtypes of sporadic renal cell carcinoma
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Mismatch repair proteins hMLH1 and hMSH2 are differently expressed in the three main subtypes of sporadic renal cell carcinoma

机译：错配修复蛋白hMLH1和hMSH2在散发性肾细胞癌的三种主要亚型中表达不同

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Objectives: We studied the role of minor mismatch repair proteins (MMR) human MutL homologue 1 (hMLH1) and human MutS homologue 2 (hMSH2) in the main subtypes of renal cell carcinoma (RCC). Methods: Expression of MMR proteins hMLH1 and hMSH2 were investigated in 166 RCC tumors, containing the main subtypes by immunohistochemistry. Furthermore, each tumor was screened for microsatellite instability (MSI) using the National Cancer Institute consensus panel for hereditary non-polyposis colon carcinoma as well as for elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) by 10 additional markers. Results: MSI was found only in 2.0% of analyzable cases and EMAST was detected only in 1 patient. hMLH1 and hMSH2 expression was reduced in 83.7 (118/141) and 51.2% (65/127) of cases, respectively, in a subtype-specific manner. None of the clear cell RCC tumors retained a high hMLH1 expression and 92.0% lost hMLH1 completely, while papillary and chromophobe RCC preserved the expression in 25.0 and 33.3% of cases (p < 0.001). Subtype specificity was also present in hMSH2 staining, where chromophobe RCC retained a high expression in 41.7% of cases, while clear cell and papillary tumors did not (29.9 and 23.1%; p = 0.01). Conclusion: MSI and EMAST are rare events in sporadic RCC, whereas diminished MMR protein expression is linked to tumor entity and might contribute to the different biological behavior of the RCC subtypes.
机译：目的：我们研究了次要错配修复蛋白（MMR）人MutL同源物1（hMLH1）和人MutS同源物2（hMSH2）在肾细胞癌（RCC）的主要亚型中的作用。方法：采用免疫组织化学方法检测166例RCC肿瘤中MMR蛋白hMLH1和hMSH2的表达。此外，使用美国国家癌症研究所共识小组针对遗传性非息肉性结肠癌以及在选定的四核苷酸重复序列（EMAST）处通过10个其他标记物提高的微卫星改变，对每个肿瘤的微卫星不稳定性（MSI）进行了筛选。结果：仅在可分析病例的2.0％中发现了MSI，仅在1例患者中发现了EMAST。 hMLH1和hMSH2表达分别以亚型特异性方式降低了83.7（118/141）和51.2％（65/127）的情况。没有透明细胞RCC肿瘤保留高的hMLH1表达，而92.0％的hMLH1完全丧失，而乳头状和发色RCC保留了25.0％和33.3％的病例中的表达（p <0.001）。亚型特异性也存在于hMSH2染色中，其中发色团RCC在41.7％的病例中保持高表达，而透明细胞和乳头状瘤则没有（29.9和23.1％; p = 0.01）。结论：MSI和EMAST是散发性RCC中的罕见事件，而MMR蛋白表达降低与肿瘤实体有关，可能与RCC亚型的不同生物学行为有关。

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