Stefansson Ingunn, Akslen Lars A, MacDonald Nicola, Ryan Andy, Das Soma, Jacobs Ian J, Salvesen Helga B
Department of Pathology, The Gade Institute, Bergen, Norway.
Clin Cancer Res. 2002 Jan;8(1):138-43.
Microsatellite instability (MSI) seems to be important in the development of various human cancers including sporadic endometrial cancer. It has previously been shown that alterations in the mismatch repair gene hMLH1 seem to be important for the development of MSI in these tumors. The role of the other mismatch repair genes hMSH2 and hMSH6 has been less well studied, but investigations on patients with hereditary nonpolyposis colorectal cancer indicate that these genes also may be involved. We therefore wanted to investigate the pattern of hMSH2 and hMSH6 expression in a prospective and population-based series of endometrial carcinomas with known hMLH1 expression and MSI status. A total of 138 patients were studied, and pathological staining was seen in 19 cases (14%) for hMLH1, 26 cases (19%) for hMSH2, and 17 cases (12.3%) for hMSH6. Pathological hMLH1 expression was more frequent among tumors with high MSI (those positive for four to five of five markers), whereas pathological expression of hMSH2 and hMSH6 was more frequent among tumors with intermediate MSI (those positive for two to three of five markers). MSI was significantly correlated with pathological expression of hMLH1 (P < 0.001), hMSH2 (P = 0.04), and hMSH6 (P = 0.001). In the group with high MSI, 14 of 16 tumors (88%) showed pathological expression for at least one of the markers. The expression of hMLH1, hMSH2, or hMSH6 did not significantly influence survival. In conclusion, pathological expression of hMLH1 does not seem to account for all tumors with a MSI-positive phenotype in this population-based series of endometrial carcinomas. Our data indicate that the other mismatch repair genes hMSH2 and hMSH6 are also involved, especially in cases with intermediate MSI.
微卫星不稳定性（MSI）在包括散发性子宫内膜癌在内的多种人类癌症的发生发展中似乎起着重要作用。此前已有研究表明，错配修复基因hMLH1的改变对于这些肿瘤中MSI的发生发展似乎至关重要。其他错配修复基因hMSH2和hMSH6的作用研究较少，但对遗传性非息肉病性结直肠癌患者的调查表明这些基因也可能参与其中。因此，我们想在一组具有已知hMLH1表达和MSI状态的前瞻性且基于人群的子宫内膜癌系列研究中，调查hMSH2和hMSH6的表达模式。共研究了138例患者，其中19例（14%）的hMLH1、26例（19%）的hMSH2和17例（12.3%）的hMSH6出现病理染色。hMLH1的病理表达在高MSI的肿瘤（五个标志物中四个至五个呈阳性的肿瘤）中更为常见，而hMSH2和hMSH6的病理表达在中度MSI的肿瘤（五个标志物中两个至三个呈阳性的肿瘤）中更为常见。MSI与hMLH1（P < 0.001）、hMSH2（P = 0.04）和hMSH6（P = 0.001）的病理表达显著相关。在高MSI组中，16例肿瘤中有14例（88%）至少有一个标志物出现病理表达。hMLH1、hMSH2或hMSH6的表达对生存率没有显著影响。总之，在这个基于人群的子宫内膜癌系列研究中，hMLH1的病理表达似乎并不能解释所有MSI阳性表型的肿瘤。我们的数据表明，其他错配修复基因hMSH2和hMSH6也参与其中，尤其是在中度MSI的病例中。
