Ruszkiewicz Andrew, Bennett Graeme, Moore James, Manavis Jim, Rudzki Barney, Shen Linda, Suthers Graeme
Institute of Medical and Veterinary Science, Tissue Pathology, Royal Adelaide Hospital, Adelaide, South Australia.
Pathology. 2002 Dec;34(6):541-7. doi: 10.1080/0031302021000035965-2.
The aim of this study was to assess the performance of immunohistochemistry using antibodies for MLH1, MSH2, MSH6 and PMS2 mismatch repair gene proteins against microsatellite instability (MSI) testing.
Tumour samples included in this study were derived from referred patients for screening for hereditary non-polyposis colorectal cancer (HNPCC) and patients who had resections for colorectal cancer that were examined at our institution. MSI was assessed at nine loci (BAT25, BAT26, BAT40, D2S123, D10S197, D17S579, D18S34, D5S346 and D17S250) in all cases. Immunohistochemistry for MLH1 and MSH2 was performed in all cases. Staining for MSH6 and PMS2 was performed in selected cases only.
There were 742 tumours including 661 colorectal lesions and 81 extracolonic tumours of the HNPCC spectrum. Among the 555 MSI-negative tumours, 554 showed an intact protein expression. Amongst the 187 MSI-positive tumours, 126 showed abnormal expression of MLH1 gene protein, 41 showed abnormal expression of MSH2 gene, three showed abnormal expression of MSH6 only, one showed abnormal expression of PMS2 gene protein only and one case showed abnormal expression of all four proteins.
Immunohistochemistry offers an alternative method for assessment of MSI status which is fast and relatively inexpensive compared with MSI testing. We achieved a sensitivity rate of 92% and specificity of 99.8% for immunohistochemistry testing assessed against the MSI testing. It has to be accepted that a small fraction of MSI-positive cases will be missed by testing with immunohistochemistry alone.
本研究旨在评估使用针对错配修复基因蛋白MLH1、MSH2、MSH6和PMS2的抗体进行免疫组化检测在微卫星不稳定性（MSI）检测中的表现。
本研究纳入的肿瘤样本来自转诊进行遗传性非息肉病性结直肠癌（HNPCC）筛查的患者以及在我院接受结直肠癌切除术的患者。所有病例均在9个位点（BAT25、BAT26、BAT40、D2S123、D10S197、D17S579、D18S34、D5S346和D17S250）评估MSI。所有病例均进行MLH1和MSH2的免疫组化检测。仅对部分病例进行MSH6和PMS2染色。
共有742个肿瘤，包括661个结直肠病变和81个HNPCC谱系的结外肿瘤。在555个MSI阴性肿瘤中，554个显示蛋白表达完整。在187个MSI阳性肿瘤中，126个显示MLH1基因蛋白异常表达，41个显示MSH2基因异常表达，3个仅显示MSH6异常表达，1个仅显示PMS2基因蛋白异常表达，1例显示所有四种蛋白均异常表达。
免疫组化提供了一种评估MSI状态的替代方法，与MSI检测相比，该方法快速且相对便宜。与MSI检测相比，免疫组化检测的灵敏度为92%，特异性为99.8%。必须承认，仅通过免疫组化检测会遗漏一小部分MSI阳性病例。
