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应用免疫组织化学方法追踪原发性不明腺癌的起源:结肠和卵巢癌作为原发部位的鉴别诊断

Tracing the origin of adenocarcinomas with unknown primary using immunohistochemistry: differential diagnosis between colonic and ovarian carcinomas as primary sites.

作者信息

Lagendijk J H, Mullink H, Van Diest P J, Meijer G A, Meijer C J

机构信息

Institute for Pathology, Free University Hospital, Amsterdam, The Netherlands.

出版信息

Hum Pathol. 1998 May;29(5):491-7. doi: 10.1016/s0046-8177(98)90065-x.

DOI:10.1016/s0046-8177(98)90065-x
PMID:9596273
Abstract

To discriminate adenocarcinoma metastases originating from either colon or ovary, a panel of immunohistochemical markers was evaluated. For this purpose, paraffin sections from 157 primary and metastatic colonic and ovarian carcinomas were immunostained. These cases were divided into a learning group of 46 colonic and 54 ovarian carcinomas and a test group of 29 colonic and 28 ovarian carcinomas, including all metastatic tumors, among which were five with unknown primary site at the time of testing. The sections were immunostained with antibodies against carcinoembryonic antigen (CEA), cytokeratin 7 (CK7), cytokeratin 20 (CK20), CA125, vimentin, and CA19.9. Staining results were expressed as the product of staining intensity and percentage of positive tumor cells. Stepwise discriminant analysis was applied on the learning set to obtain a classification function for both tumors. The validity of the classification function was evaluated using the test set. There was considerable overlap in immunostaining for both tumor types, but colonic carcinomas were typically positive for CEA and CK20 and negative for CK7 and CA125. Ovarian carcinomas were typically positive for CK7 and CA125 and negative for CEA and CK20. In discriminant analysis, the best combination of markers appeared to be CK7 and CEA. Only one sample of the test group (2%) was misclassified. Taking learning and test groups together, 136 of the 157 samples (87%) were correctly classified with high posterior probability (PP > .8). However, from the 28 mucinous ovarian carcinomas, only 19 (68%) could correctly be classified with high PP. When excluding the nonmucinous ovarian carcinomas from the analysis, overall 87 of 103 (84.5%) of the samples were correctly classified (PP > .8) with a combination of CEA, CK7, and also vimentin. From the 28 mucinous ovarian carcinomas, only two (7%) were misclassified, and four could not be classified with sufficient certainty. In neither analysis did CK20, CA125, or CA19.9 emerge as discriminatory parameters. Based on the same data, an intuitive flow chart was constructed with which 129 of 157 cases could be classified (only one falsely) without further statistical analysis. The five metastases with an at first unknown primary could, according to the follow-up, all be classified correctly with high PP. Most ovarian carcinomas, including the mucinous ones, can be discriminated with high probability from colonic carcinomas using a panel of three antibodies directed against CEA, cytokeratin 7, and vimentin.

摘要

为鉴别源自结肠或卵巢的腺癌转移灶,对一组免疫组化标志物进行了评估。为此,对157例原发性及转移性结肠和卵巢癌的石蜡切片进行了免疫染色。这些病例被分为一个学习组,包括46例结肠癌和54例卵巢癌,以及一个测试组,包括29例结肠癌和28例卵巢癌,其中包括所有转移瘤,测试时其中5例原发部位不明。切片用抗癌胚抗原(CEA)、细胞角蛋白7(CK7)、细胞角蛋白20(CK20)、CA125、波形蛋白和CA19.9的抗体进行免疫染色。染色结果表示为染色强度与阳性肿瘤细胞百分比的乘积。对学习集应用逐步判别分析以获得两种肿瘤的分类函数。使用测试集评估分类函数的有效性。两种肿瘤类型的免疫染色有相当程度的重叠,但结肠癌通常CEA和CK20阳性,CK7和CA125阴性。卵巢癌通常CK7和CA125阳性,CEA和CK20阴性。在判别分析中,最佳标志物组合似乎是CK7和CEA。测试组中只有一个样本(2%)被错误分类。将学习组和测试组合并,157个样本中有136个(87%)以高后验概率(PP>.8)被正确分类。然而,在28例黏液性卵巢癌中,只有19例(68%)能以高PP正确分类。当从分析中排除非黏液性卵巢癌时,总体上103个样本中的87个(84.5%)通过CEA、CK7以及波形蛋白的组合被正确分类(PP>.8)。在28例黏液性卵巢癌中,只有2例(7%)被错误分类,4例无法得到足够确定的分类。在任何分析中,CK20、CA125或CA19.9都未成为鉴别参数。基于相同数据构建了一个直观的流程图,无需进一步统计分析即可对157例中的129例进行分类(仅1例错误)。根据随访情况,最初原发部位不明的5个转移灶均能以高PP正确分类。使用一组针对CEA、细胞角蛋白7和波形蛋白的三种抗体,大多数卵巢癌,包括黏液性卵巢癌,都能以高概率与结肠癌鉴别开来。

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