Department of Pathology, University of Iowa Hospitals and Clinics and Carver College of Medicine, Iowa City, IA, USA.
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Histopathology. 2018 Jul;73(1):162-166. doi: 10.1111/his.13483. Epub 2018 Apr 19.
Merkel cell carcinoma represents poorly differentiated neuroendocrine carcinoma of cutaneous origin. In most studies, the vast majority of Merkel cell carcinomas are Merkel cell polyomavirus (MCPyV)-associated. SV40 polyomavirus immunohistochemistry is typically used in the diagnosis of other polyomavirus-associated diseases, including tubulointerstitial nephritis and progressive multifocal leukoencephalopathy, given cross-reactivity with BK and JC polyomaviruses. MCPyV-specific immunohistochemistry is commercially available, but, if antibodies against SV40 also cross-reacted with MCPyV, that would be advantageous from a resource-utilisation perspective.
Tissue microarrays were constructed from 39 Merkel cell carcinomas, 24 small-cell lung carcinomas, and 18 extrapulmonary visceral small-cell carcinomas. SV40 large T antigen immunohistochemistry (clone PAb416) was performed; MCPyV large T antigen immunohistochemistry (clone CM2B4) had been previously performed. UniProt was used to compare the amino acid sequences of the SV40, BK, JC and MCPyV large T antigens, focusing on areas recognised by the PAb416 and CM2B4 clones. SV40 immunohistochemistry was negative in all tumours; MCPyV immunohistochemistry was positive in 38% of Merkel cell carcinomas and in 0% of non-cutaneous poorly differentiated neuroendocrine carcinomas. UniProt analysis revealed a high degree of similarity between SV40, BK, and JC viruses in the region recognised by PAb416. There was less homology between SV40 and MCPyV in this region, which was also interrupted by two long stretches of amino acids unique to MCPyV. The CM2B4 clone recognises a unique epitope in one of these stretches.
The PAb416 antibody against the SV40 large T antigen does not cross-react with MCPyV large T antigen, and thus does not label Merkel cell carcinoma.
默克尔细胞癌是一种起源于皮肤的低分化神经内分泌癌。在大多数研究中，绝大多数默克尔细胞癌与默克尔细胞多瘤病毒（MCPyV）相关。由于与 BK 和 JC 多瘤病毒存在交叉反应性，SV40 多瘤病毒免疫组化通常用于其他多瘤病毒相关疾病的诊断，包括肾小管间质性肾炎和进行性多灶性白质脑病。MCPyV 特异性免疫组化可商购获得，但如果针对 SV40 的抗体也与 MCPyV 发生交叉反应，从资源利用的角度来看，这将是有利的。
从 39 例默克尔细胞癌、24 例小细胞肺癌和 18 例肺外内脏小细胞癌中构建组织微阵列。进行 SV40 大 T 抗原免疫组化（克隆 PAb416）；先前进行了 MCPyV 大 T 抗原免疫组化（克隆 CM2B4）。UniProt 用于比较 SV40、BK、JC 和 MCPyV 大 T 抗原的氨基酸序列，重点是 PAb416 和 CM2B4 克隆识别的区域。所有肿瘤的 SV40 免疫组化均为阴性；38%的默克尔细胞癌和 0%的非皮肤低分化神经内分泌癌的 MCPyV 免疫组化阳性。UniProt 分析显示，在 PAb416 识别的区域，SV40、BK 和 JC 病毒之间具有高度相似性。在该区域，SV40 与 MCPyV 的同源性较低，该区域还被 MCPyV 特有的两个长氨基酸序列打断。CM2B4 克隆识别其中一个长氨基酸序列中的独特表位。
针对 SV40 大 T 抗原的 PAb416 抗体与 MCPyV 大 T 抗原不发生交叉反应，因此不会标记默克尔细胞癌。
