Mismatch repair genes hMLH1 and hMSH2 may not play an essential role in breast carcinogenesis
Mismatch repair genes hMLH1 and hMSH2 may not play an essential role in breast carcinogenesis
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DOI：
10.1177/1066896907302116
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发表时间：
2007-07-01
影响因子：
1.2
通讯作者：
Tang, Ping
中科院分区：
文献类型：
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作者：
Khilko, Natalya;Bourne, Patricia;Tang, Ping
乳腺癌是女性最常见的恶性肿瘤之一，其致癌机制尚不清楚。微卫星不稳定性(MSI)在乳腺癌发生中的作用在文献中一直不一致。应用免疫组织化学方法检测了211例乳腺导管内癌(DCIS；90例)和121例乳腺浸润性导管癌(浸润性导管癌)组织中hMLH1和hMSH2的表达，并探讨其与细胞角蛋白(CK)亚型、ER-a(138例阳性、73例阴性)、PR(118例阳性、93例阴性)、HER-2/neu(47例阳性、164例阴性)、患者年龄(157例、50岁、54例、50岁)、肿瘤大小(31例)、肿瘤大小(31例)等临床特征的关系。肿瘤分级(高核级87例，非高级别124例)和有无淋巴结转移(IDC阳性38例，IDC阴性74例，IDC无淋巴结转移9例)。CK亚型中，167例为管腔型(表达CK8和/或CK18，CK5/6、CK14、CK17阴性)，44例为非管腔型(多为基底型/干型，表达CK5/6和/或CK14、和/或CK17)。本研究没有纳入典型或不典型的髓样癌。我们的结果显示，在211例DCIS或IDC中，无论何种病理和临床因素，均未发现hMLH1或hMSH2的核表达缺失，提示hMLH1或hMSH2在大多数乳腺癌中可能不起重要作用。
Breast carcinoma is one of the most common malignancies in women, and its carcinogenesis is still unknown. The role of microsatellite instability (MSI) in breast carcinogenesis has been inconsistent in the literature. Here we studied the expression of 2 mismatch repair genes, hMLH1 and hMSH2, in 211 cases of intraductal (DCIS; 90 cases) and invasive ductal carcinoma (121 cases) of the breast by immunohistochemical analysis; and evaluated its relationship with cytokeratin (CK) subtypes, along with expression of ER-a (138 cases positive, 73 cases negative); PR (118 cases positive, 93 cases negative), and HER-2/neu (47 cases positive, 164 cases negative); and clinical features such as patient age (157 cases > 50 years, 54 cases < 50 years), tumor size (31 cases of IDC > 2 cm, 90 cases of IDC < 2 cm), tumor grade (87 cases high nuclear grade, 124 case non-high grade), and lymph node metastasis (38 cases of IDC positive, 74 cases of IDC negative, 9 cases of IDC with no available data on lymph node status). For CK subtypes, 167 cases were classified as luminal subtype (expressing CK8 and/or CK18, negative for CK5/6, CK14, and CK17) and 44 cases were classified as nonluminal (most of them belonged to basal/stem subtype, expressing CK5/6, and/or CK14, and/or CK17). No typical or atypical medullary carcinoma was included in this study. Our results showed that no loss of nuclear expression of either hMLH1 or hMSH2 was identified in any of the 211 cases of DCIS or IDC regardless of the various pathological and clinical factors, suggesting that hMLH1 or hMSH2 may not play an essential role in the majority of cases of the breast carcinoma.