Microsatellite instability and alteration of the expression of hMLH1 and hMSH2 in ovarian clear cell carcinoma
Microsatellite instability and alteration of the expression of hMLH1 and hMSH2 in ovarian clear cell carcinoma
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DOI：
10.1016/j.humpath.2003.12.009
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发表时间：
2004-05-01
期刊：
影响因子：
3.3
通讯作者：
Liu, JS
中科院分区：
文献类型：
--
作者：
Cai, KQ;Albarracin, C;Liu, JS
微卫星不稳定性（MSI）常见于与遗传性非息肉病性结直肠癌综合征相关的肿瘤中，由DNA错配修复基因缺陷引起。MSI还在各种散发性癌症中观察到，包括结直肠癌、胃癌和子宫内膜癌。MSI在卵巢透明细胞癌中的作用和发生率尚不清楚。本研究旨在评估卵巢透明细胞癌中MSI的频率，并评估免疫组化预测错配修复基因缺陷的敏感性和特异性。共42例卵巢透明细胞癌的MSI分析使用了一组5个微卫星标记（BAT 25，BAT 26，D5 S346，D2 S123和D17 S250）。检测这些肿瘤中hMLH 1和hMSH 2蛋白表达的变化。在42例卵巢透明细胞肿瘤中，6例表现出高水平的MSI（MSI-H），3例表现出低水平的MSI（MSI-L），其余33例表现出微卫星稳定性（MSS）。MSI水平与患者年龄、肿瘤分期、肿瘤大小无相关性（P>0.05）。6例MSI-H肿瘤中有4例（67.7%）hMLH 1或hMSH 2表达缺失，而36例MSI-L或MSS肿瘤中有34例（94.4%）hMLH 1和hMSH 2基因产物均表达。我们的研究结果表明，MSI-H参与了卵巢透明细胞癌的一个子集的发展。在这些肿瘤中，hMLH 1和hMSH 2表达的改变与MSI-H的存在之间存在很强的相关性。然而，免疫组化检测可能会错过一小部分MSI-H病例。第35章552-559. (C)2004年爱思唯尔公司All rights reserved.
Microsatellite instability (MSI) is commonly seen in tumors associated with the hereditary nonpolyposis colorectal cancer syndrome and is caused by defects in the DNA mismatch repair genes. MSI has also been observed in various sporadic cancers, including colorectal, gastric, and endometrial. The role and incidence of MSI in ovarian clear cell carcinoma remain unknown. This study was conducted to evaluate the frequency of MSI in ovarian clear cell carcinomas and to evaluate the sensitivity and specificity of immunohistochemistry in predicting mismatch-repair gene deficiency. A total of 42 ovarian clear cell carcinomas were analyzed for MSI using a panel of 5 microsatellite markers (BAT25, BAT26, D5S346, D2S123, and D17S250). Alterations in the expression of hMLH1 and hMSH2 proteins in these tumors were examined. Of the 42 ovarian clear cell tumors analyzed, 6 demonstrated a high level of MSI (MSI-H), 3 demonstrated a low level of MSI (MSI-L), and the remaining 33 exhibited microsatellite stability (MSS). No correlation was found between MSI level and patient age or tumor stage or size (P>0.05). Loss of expression of either hMLH1 or hMSH2 was observed in 4 of the 6 (67.7%) MSI-H tumors, whereas 34 of the 36 (94.4%) MSI-L or MSS tumors expressed both the hMLH1 and hMSH2 gene products. Our results indicate that MSI-H is involved in the development of a subset of ovarian clear cell carcinomas. A strong correlation exists between alterations in the expression of hMLH1 and hMSH2 and the presence of MSI-H in these tumors. However, immunohistochemical testing alone may miss a small fraction of cases with MSI-H. Hum PATHOL 35:552-559. (C) 2004 Elsevier Inc. All rights reserved.