Modica Ippolito, Soslow Robert A, Black Destin, Tornos Carmen, Kauff Noah, Shia Jinru
Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Am J Surg Pathol. 2007 May;31(5):744-51. doi: 10.1097/01.pas.0000213428.61374.06.
Identification of the microsatellite instability (MSI) phenotype in endometrial carcinoma is important given that such tumors are the most common noncolorectal tumors to occur in hereditary nonpolyposis colorectal cancer syndrome, and may bear prognostic relevance. The objective of this study was to assess the utility of immunohistochemistry (IHC), a simple and fast technique, in detecting MSI in endometrial carcinoma. The study subjects consisted of 90 endometrial carcinoma patients with equal representation of MSI-high (MSI-H) and non-MSI-H tumors. MSI was tested using the standard polymerase chain reaction-based method and the 5 NCI-recommended markers. Overall, IHC with MLH1 and MSH2 antibodies detected 69% of MSI-H tumors with a specificity of 100%. Adding PMS2 and MSH6 to the antibody panel increased the sensitivity to 91% but decreased the specificity to 83%. The most common IHC abnormality in MSI tumors was concurrent loss of MLH1/PMS2. Assessment of staining was straightforward in most cases but not in all. Staining inadequacies existed. Five stains (4 MLH1 and 1 MSH6) were not interpretable because of the lack of any internal positive control. Two percent to 10% of the cases (depending on the antibody assessed) had only focal weak staining; the highest frequency (10%) occurred with MLH1 antibody. PMS2 staining detected 7 MLH1-staining present MSI-H cases, thus partly accounting for the increased sensitivity with the 4-antibody panel. MSH6 staining identified 9 cases with loss of MSH6 alone, 6 of 9 were non-MSI-H, thus partly accounting for the decreased specificity with the 4-antibody panel. In conclusion, our results suggest that IHC is useful in detecting MSI in endometrial carcinoma. Although IHC has a lower sensitivity with more apparent staining inadequacies in detecting MSI in endometrial carcinoma than it does in colorectal carcinoma, its use in endometrial carcinoma may be an important adjunct when screening for hereditary cases. In the future, as prognostic and therapeutic implications of MSI phenotype become better defined, it may be reasonable to perform IHC for mismatch repair proteins in large numbers of endometrial carcinomas.
鉴于子宫内膜癌是遗传性非息肉病性结直肠癌综合征中最常见的非结直肠癌肿瘤，且可能具有预后相关性，因此识别子宫内膜癌中的微卫星不稳定性（MSI）表型很重要。本研究的目的是评估免疫组织化学（IHC）这种简单快速的技术在检测子宫内膜癌MSI中的实用性。研究对象包括90例子宫内膜癌患者，MSI高（MSI-H）肿瘤和非MSI-H肿瘤各占一半。使用基于标准聚合酶链反应的方法和5种美国国立癌症研究所（NCI）推荐的标志物检测MSI。总体而言，使用MLH1和MSH2抗体进行免疫组织化学检测出69%的MSI-H肿瘤，特异性为100%。在抗体组合中加入PMS2和MSH6可将敏感性提高到91%，但特异性降至83%。MSI肿瘤中最常见的免疫组织化学异常是MLH1/PMS2同时缺失。在大多数情况下，染色评估很简单，但并非所有情况都是如此。存在染色不足的情况。由于缺乏任何内部阳性对照，5次染色（4次MLH1和1次MSH6）无法解读。2%至10%的病例（取决于评估的抗体）仅有局灶性弱阳性染色；MLH1抗体出现的频率最高（10%）。PMS2染色检测出7例MLH1染色阳性的MSI-H病例，因此部分解释了4抗体组合敏感性增加的原因。MSH6染色识别出9例单独MSH6缺失的病例，其中6例为非MSI-H，因此部分解释了4抗体组合特异性降低的原因。总之，我们的结果表明免疫组织化学在检测子宫内膜癌MSI中是有用的。尽管免疫组织化学在检测子宫内膜癌MSI方面比在结直肠癌中敏感性更低，染色不足更明显，但其在子宫内膜癌中的应用可能是筛查遗传性病例时的一项重要辅助手段。未来，随着MSI表型的预后和治疗意义得到更明确的定义，对大量子宫内膜癌进行错配修复蛋白的免疫组织化学检测可能是合理的。
