Microsatellite instability and hMLH1 and hMSH2 expression in renal tumors
Microsatellite instability and hMLH1 and hMSH2 expression in renal tumors
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DOI：
10.3892/or_00000938
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发表时间：
2010-10-01
期刊：
影响因子：
4.2
通讯作者：
Giacomelli, Luciano
中科院分区：
文献类型：
--
作者：
Altavilla, Giuseppe;Fassan, Matteo;Giacomelli, Luciano
错配修复(MMR)基因的功能缺陷会导致遗传不稳定，这是恶性进展的常见特征。本研究旨在确定遗传不稳定[定义为微卫星不稳定(MSI)]的频率，并评价免疫组织化学在预测肾皮质肿瘤MMR基因缺陷方面的敏感性/特异性。共51例经手术切除的肾肿瘤(透明细胞瘤27例，乳头状瘤10例，嫌色细胞癌5例，嗜酸细胞瘤9例)进行了研究。我们还分析了与临床病理参数、MSI状态(通过5个微卫星标记：D2S123、D11S904、D3S1621、D3S1683和BAT26来评估)以及两个主要MMR基因[人类MMR同源基因1(HMLHI)和人类MutS同源基因2(HMSH2)]的相关性。MSI 16例(31.4%)，其中高MSI 3例(5.9%)，低MSI 11例(21.6%)，杂合性缺失2例(3.9%)，其余35例(68.6%)表现为微卫星稳定性。免疫组织化学hMLH1和hMSH2表达缺失率分别为9.8%(5/51)和17.6%(9/51)。HMLH1和hMSH2免疫组织化学仅在3例MSI较高的病例中均无表达。本研究表明MMR基因缺陷与肾癌的发生有关，并与MSI的发生有关。
Defects in the function of mismatch repair (MMR) genes result in genetic instability, a common feature of malignant progression. This study was conducted to determine the frequency of genetic instability [defined as microsatellite instability (MSI)] and to evaluate the sensitivity/specificity of immunohistochemistry in predicting the deficiency in MMR genes in renal cortical tumors. A total of 51 surgically-resected renal tumors (27 clear cell, 10 papillary, 5 chromophobe carcinomas and 9 oncocytomas) were studied. We also analyzed the correlation with clinicopathological parameters, the MSI status (assessed by using 5 microsatellite markers: D2S123, D11S904, D3S1621, D3S1683 and BAT26), and the immunohistochemical expression of 2 major MMR genes [the human mutL homolog 1 (hMLHI) and the human mutS homolog 2 (hMSH2)]. Sixteen cases (31.4%) showed MSI: Three (5.9%) demonstrated a high level of MSI, 11 (21.6%) demonstrated a low level of MSI, 2 (3.9%) presented with a loss of heterozygosity, and the remaining 35 (68.6%) exhibited microsatellite stability. The loss of hMLH1 and hMSH2 immunohistochemical expressions was observed in 5/51 (9.8%) and 9/51 (17.6%) cases, respectively. The complete absence of both hMLH1 and hMSH2 immunohistochemical expressions was observed only in the 3 cases with a high level of MSI. This study showed that defects in MMR genes are involved in renal carcinogenesis and correlate with the occurrence of MSI.