Utility of immunohistochemistry in predicting microsatellite instability in endometrial carcinoma
Utility of immunohistochemistry in predicting microsatellite instability in endometrial carcinoma
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DOI：
10.1097/01.pas.0000213428.61374.06
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发表时间：
2007-05-01
影响因子：
5.6
通讯作者：
Shia, Jinru
中科院分区：
文献类型：
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作者：
Modica, Ippolito;Soslow, Robert A.;Shia, Jinru
子宫内膜癌中微卫星不稳定性（MSI）表型的鉴定是重要的，因为这种肿瘤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肿瘤，并可能与预后相关。本研究的目的是评估免疫组化（IHC），一种简单，快速的技术，在检测子宫内膜癌MSI的效用。研究对象由90名子宫内膜癌患者组成，其中MSI高（MSI-H）和非MSI-H肿瘤的代表性相等。MSI采用标准的聚合酶链反应方法和5种NCI推荐的标记物进行检测。总体而言，使用MLH 1和MSH 2抗体的IHC检测到69%的MSI-H肿瘤，特异性为100%。将PMS 2和MSH 6添加到抗体组中使灵敏度增加到91%，但使特异性降低到83%。MSI肿瘤中最常见的免疫组化异常是MLH 1/PMS 2的同时丢失。在大多数情况下，染色评估是简单的，但不是所有情况下。存在染色不足。由于缺乏任何内部阳性对照，5种染色（4种MLH 1和1种MSH 6）无法判读。2%至10%的病例（取决于评估的抗体）仅出现局灶性弱染色; MLH 1抗体出现的频率最高（10%）。PMS 2染色检测到7例MLH 1染色存在MSI-H病例，因此部分解释了4抗体组的灵敏度增加。MSH 6染色鉴定了9例MSH 6单独缺失的病例，9例中有6例是非MSI-H，因此部分解释了4抗体组特异性降低的原因。总之，我们的研究结果表明，免疫组化是有用的检测MSI在子宫内膜癌。虽然IHC在检测子宫内膜癌MSI方面的敏感性较低，且染色不足较明显，但在筛查遗传性病例时，其在子宫内膜癌中的应用可能是一个重要的辅助手段。在未来，随着MSI表型的预后和治疗意义变得更好地定义，在大量子宫内膜癌中对错配修复蛋白进行IHC可能是合理的。
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.