Shih I M, Nesbit M, Herlyn M, Kurman R J
Department of Pathology, The Johns Hopkins Medical Institution, Baltimore, Maryland, USA.
Mod Pathol. 1998 Nov;11(11):1098-106.
Mel-CAM (also termed CD146 or MUC18) is a cell-adhesion molecule belonging to the immunoglobulin gene superfamily. It mediates cell-cell interaction through heterophilic Mel-CAM/ligand adhesion. Previous studies showed Mel-CAM immunoreactivity in normal and neoplastic human tissues, but an extensive assessment of Mel-CAM distribution was not performed because of the lack of a Mel-CAM-specific monoclonal antibody that could be used in routinely processed, formalin-fixed, paraffin-embedded tissues. Therefore, we developed a mouse monoclonal antibody, MN-4, that specifically recognized a fixation-resistant epitope in the second extracellular (C2) domain of Mel-CAM. We performed immunohistochemical staining on 467 paraffin-embedded tissue samples with this MN-4 antibody and avidin-biotin peroxidase. MN-4 immunoreactivity was seen in normal tissues, including endothelium, smooth muscle, epithelial and myoepithelial cells of the breast, Schwann cells, ganglion cells, cerebellar cortex, implantation-site intermediate trophoblast, external root sheath of hair follicles, basal cells of bronchial epithelium, parathyroid glands, subcapsular epithelium of thymus, follicular dendritic reticulum cells, skeletal muscles, epithelium of lens, and glial cell fibers in the central nervous system in early embryos. In malignant tumors, MN-4 immunostaining was consistently present in all melanomas, angiosarcomas, Kaposi's sarcomas, leiomyosarcomas, mucoepidermoid carcinomas of salivary gland, placental-site trophoblastic tumors, and choriocarcinomas. Three of 8 squamous cell carcinomas, 2 of 2 small cell carcinomas of the lung, 2 of 11 of infiltrating breast carcinomas, and 4 of 11 of germinomas were focally and weakly positive for MN-4 antibody. In contrast, a wide variety of other carcinomas, sarcomas, lymphomas, leukemias, and neuroendocrine tumors failed to show MN-4 immunoreactivity. In conclusion, MN-4 is a specific monoclonal antibody that recognizes Mel-CAM on paraffin sections. This antibody is useful in retrospective studies of Mel-CAM expression in archival tissue sections and might provide a diagnostic and prognostic marker for human neoplasms.
黑色素瘤细胞粘附分子（也称为CD146或MUC18）是一种属于免疫球蛋白基因超家族的细胞粘附分子。它通过嗜异性黑色素瘤细胞粘附分子/配体粘附介导细胞间相互作用。先前的研究显示黑色素瘤细胞粘附分子在正常和肿瘤性人类组织中有免疫反应性，但由于缺乏可用于常规处理的福尔马林固定石蜡包埋组织的黑色素瘤细胞粘附分子特异性单克隆抗体，因此未对黑色素瘤细胞粘附分子的分布进行广泛评估。因此，我们开发了一种小鼠单克隆抗体MN-4，它能特异性识别黑色素瘤细胞粘附分子第二细胞外（C2）结构域中的一个抗固定表位。我们用这种MN-4抗体和抗生物素蛋白-生物素过氧化物酶对467份石蜡包埋组织样本进行了免疫组织化学染色。MN-4免疫反应性见于正常组织，包括内皮细胞、平滑肌、乳腺的上皮和肌上皮细胞、施万细胞、神经节细胞、小脑皮质、着床部位的中间滋养层细胞、毛囊外根鞘、支气管上皮基底细胞、甲状旁腺、胸腺被膜下上皮、滤泡性树突状网状细胞、骨骼肌、晶状体上皮以及早期胚胎中枢神经系统中的胶质细胞纤维。在恶性肿瘤中，MN-4免疫染色始终存在于所有黑色素瘤、血管肉瘤、卡波西肉瘤、平滑肌肉瘤、涎腺黏液表皮样癌、胎盘部位滋养细胞肿瘤和绒毛膜癌中。8例鳞状细胞癌中有3例、2例肺小细胞癌中有2例、11例浸润性乳腺癌中有2例以及11例生殖细胞瘤中有4例对MN-4抗体呈局灶性弱阳性。相比之下，多种其他癌、肉瘤、淋巴瘤、白血病和神经内分泌肿瘤未显示MN-4免疫反应性。总之，MN-4是一种能识别石蜡切片上黑色素瘤细胞粘附分子的特异性单克隆抗体。该抗体可用于存档组织切片中黑色素瘤细胞粘附分子表达的回顾性研究，并可能为人类肿瘤提供诊断和预后标志物。
