Hanley Krisztina Z, Facik Michael S, Bourne Patricia A, Yang Qi, Spaulding Betsy O, Bonfiglio Thomas A, Xu Haodong
Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York 14642, USA.
Cancer. 2008 Feb 25;114(1):49-56. doi: 10.1002/cncr.23254.
Immunohistochemistry is helpful in distinguishing metastatic carcinoma from atypical mesothelial cells; however, it is not useful in differentiating atypical mesothelial cells from malignant mesothelial cells. K homolog domain containing protein overexpressed in cancer (KOC), a member of the insulin-like growth factor mRNA-binding protein (IMP) family, also known as L523S and IMP3, is expressed during embryogenesis and in various malignancies. Using a mouse monoclonal antibody (L523S) against KOC, KOC expression was investigated in malignant tumors and reactive mesothelial cells in serous effusions.
Seventy-six cases with paraffin-embedded pleural, pericardial, and peritoneal serous effusion cell blocks including 60 malignant serous effusions (11 malignant pleural mesotheliomas and 49 metastatic carcinomas) and benign pleural effusions (14 cases with reactive mesothelial cells and 2 cases with atypical cells with uncertain significance) were selected for immunohistochemical analysis with L523S, calretinin, and CK5/6.
Immunohistochemical studies showed that positive staining for KOC of variable degrees of intensity was observed in 47 of 60 cases in malignant serous effusions including 10 of 11 mesotheliomas and 36 of 49 metastatic carcinomas. The associated reactive mesothelial cells were negative for KOC but positive for calretinin and CK5/6. All 11 malignant mesotheliomas exhibited positivity for calretinin, and 9 of 11 cases had CK5/6 staining. In addition, 16 cases that were originally diagnosed either as pleural effusions with reactive mesothelial cells (14) or atypical cells with uncertain significance (2) were also tested for KOC expression. Interestingly, 3 of 16 cases exhibited various degrees of positivity for KOC, 2 of which were diagnosed as lung adenocarcinoma with a recurrence after tumor resection and 1 as malignant pleural mesothelioma.
Anti-L523S antibody is a useful marker for the detection of malignant cells in serous effusions and it can have significant utility in differentiating reactive mesothelial cells from malignant mesothelioma and metastatic carcinoma in combination with calretinin and CK5/6 staining.
免疫组织化学有助于鉴别转移性癌与非典型间皮细胞;然而,它在区分非典型间皮细胞与恶性间皮细胞方面并无用处。癌症中过表达的含K同源结构域蛋白(KOC)是胰岛素样生长因子mRNA结合蛋白(IMP)家族的一员,也被称为L523S和IMP3,在胚胎发育过程及多种恶性肿瘤中表达。使用针对KOC的小鼠单克隆抗体(L523S),研究了浆液性积液中恶性肿瘤及反应性间皮细胞的KOC表达情况。
选取76例石蜡包埋的胸膜、心包和腹膜浆液性积液细胞块,包括60例恶性浆液性积液(11例恶性胸膜间皮瘤和49例转移性癌)以及良性胸腔积液(14例反应性间皮细胞和2例意义不明确的非典型细胞),采用L523S、钙视网膜蛋白和细胞角蛋白5/6进行免疫组织化学分析。
免疫组织化学研究显示,60例恶性浆液性积液中的47例观察到不同强度的KOC阳性染色,包括11例间皮瘤中的10例和49例转移性癌中的36例。相关的反应性间皮细胞KOC呈阴性,但钙视网膜蛋白和细胞角蛋白5/6呈阳性。所有11例恶性间皮瘤钙视网膜蛋白均呈阳性,11例中有9例细胞角蛋白5/6染色阳性。此外,对最初诊断为反应性间皮细胞的胸腔积液(14例)或意义不明确的非典型细胞(2例)的16例病例也进行了KOC表达检测。有趣的是,16例中有3例KOC呈不同程度阳性,其中2例诊断为肺腺癌,肿瘤切除后复发,1例诊断为恶性胸膜间皮瘤。
抗L523S抗体是检测浆液性积液中恶性细胞的有用标志物,与钙视网膜蛋白和细胞角蛋白5/6染色联合使用,在区分反应性间皮细胞与恶性间皮瘤及转移性癌方面具有重要作用。