Merkel cell polyomavirus expression in merkel cell carcinomas and its absence in combined tumors and pulmonary neuroendocrine carcinomas.
Merkel cell polyomavirus expression in merkel cell carcinomas and its absence in combined tumors and pulmonary neuroendocrine carcinomas.
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DOI：
10.1097/pas.0b013e3181aa30a5
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发表时间：
2009-09
期刊：
影响因子：
--
通讯作者：
Chang Y
中科院分区：
文献类型：
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作者：
Busam KJ;Jungbluth AA;Rekthman N;Coit D;Pulitzer M;Bini J;Arora R;Hanson NC;Tassello JA;Frosina D;Moore P;Chang Y
默克尔细胞癌（MCC）是原发性皮肤神经内分泌癌的同名词。最近，一种新的多瘤病毒被发现，它克隆整合到大多数 MCC 的基因组中，病毒大 T 抗原基因发生截短突变。我们通过定量聚合酶链式反应检测了一组 17 个冷冻肿瘤样本中是否存在默克尔细胞多瘤病毒 (MCV)；其中 15 例（88%）呈阳性。使用针对 MCV T 抗原上的预测抗原表位生成的新型单克隆抗体 CM2B4 通过免疫组织化学 (IHC) 分析相应档案材料的切片，并测试细胞角蛋白 20 (CK20) 的表达。在通过聚合酶链式反应研究冷冻组织样本的 17 例病例中，只有 15 例具有足够的 IHC 档案材料。在免疫组织化学分析的 15 个肿瘤中，10 个（67%）显示 CM2B4 阳性标记，14 个（93%）表达 CK20。还通过 IHC 检查了 36 个 MCC、7 个皮肤鳞状细胞癌和神经内分泌癌组合以及 26 个肺神经内分泌癌的组织微阵列。在微阵列上组装的 36 个 MCC 中，32 个 (89%) 肿瘤表达 CK20，27 个 (75%) 肿瘤与 CM2B4 发生免疫反应。具有鳞状和神经内分泌组合表型的皮肤肿瘤以及所有肺神经内分泌癌均未能与 CM2B4 发生反应。我们的研究表明 CM2B4 是诊断 MCC 的有用试剂。它可以标记大多数 MCC，但无法与肺神经内分泌癌发生反应。我们还发现，与鳞状细胞癌相关的皮肤神经内分泌癌似乎与 MCV 无关。
Merkel cell carcinoma (MCC) is the eponym for primary cutaneous neuroendocrine carcinoma. Recently, a new polyoma virus has been identified that is clonally integrated in the genome of the majority of MCCs, with truncating mutations in the viral large T antigen gene. We examined the presence of Merkel cell polyomavirus (MCV) in a set of 17 frozen tumor samples by quantitative polymerase chain reaction; 15 of them (88%) were positive. Sections from corresponding archival material were analyzed by immunohistochemistry (IHC) with the novel monoclonal antibody CM2B4, generated against a predicted antigenic epitope on the MCV T antigen, and tested for the expression of cytokeratin 20 (CK20). Sufficient archival material for IHC was available in only 15 of the 17 cases whose frozen tissue samples had been studied by polymerase chain reaction. Of the 15 tumors analyzed immunohistochemically, 10 (67%) showed positive labeling with CM2B4, 14 (93%) expressed CK20. A tissue microarray of 36 MCCs, 7 combined squamous and neuroendocrine carcinomas of the skin, and 26 pulmonary neuroendocrine carcinomas were also examined by IHC. Of the 36 MCCs assembled on a microarray, 32 (89%) tumors expressed CK20, and 27 (75%) were immunoreactive with CM2B4. The skin tumors with a combined squamous and neuroendocrine phenotype and all pulmonary neuroendocrine carcinomas failed to react with CM2B4. Our study shows that CM2B4 is a useful reagent for the diagnosis of MCC. It labels the majority of MCCs, but fails to react with pulmonary neuroendocrine carcinomas. We also found that neuroendocrine carcinomas of the skin arising in association with a squamous cell carcinoma seem to be independent of MCV.