Szent István University, Faculty of Veterinary Sciences, Department of Pathology and Forensic Veterinary Medicine, Budapest, Hungary.
Histol Histopathol. 2012 Jul;27(7):905-17. doi: 10.14670/HH-27.905.
A peripheral nerve sheath tumour consists of neoplastic Schwann cells or perineurial cells, or a mixture of Schwann cells, perineurial cells and fibroblasts. The first aim of the present study was to characterise the expression of the claudin-1 tight junction protein in canine intact peripheral nerves, canine benign peripheral nerve sheath tumours (cBPNSTs), such as schwannomas, neurofibromas, perineuriomas and canine malignant peripheral nerve sheath tumours (cMPNSTs), and in different other benign and malignant canine spindle cell tumours. The second aim of the present study was to examine whether claudin-1 can help to distinguish the subgroups of canine perivascular wall tumours.
The biopsy and necropsy samples (n=203) included 10 intact peripheral nerves, 20 cBPNSTs (4 schwannomas, 8 neurofibromas, 8 perineuriomas), 16 cMPNSTs, 6 psammomatous meningiomas, 6 dermatofibromas, 6 leiomyomas, 6 myxomas, 4 spindle cell hemangiomas, 2 spindle cell lipomas, 6 fibrohistiocytic nodules, 8 fibrosarcomas, 8 leiomyosarcomas, 6 myxosarcomas, 8 hemangiosarcomas, 8 anaplastic sarcomas, 8 amelanotic spindle cell melanomas, 8 histiocytic sarcomas, 8 spindle cell carcinomas, 8 myoepitheliomas, 8 complex carcinomas, 5 cardiac rhabdomyosarcomas, 4 synovial sarcomas, 5 osteosarcomas, 4 chondrosarcomas and 4 liposarcomas; 31 canine perivascular wall tumours: 10 hemangiopericytomas, 8 myopericytomas, 6 angioleiomyomas, 4 angioleiomyosarcomas, 3 angiofibromas. The immunohistochemical panel consisted of humanized antibodies: anti-claudin-1, anti-neuron specific enolase, anti-S-100 protein, anti-α-smooth muscle actin, anti-vimentin, anti-cytokeratin AE1-AE3, anti-claudin-5, anti-Melan-A and anti-heavy caldesmon, anti-calponin and anti-desmin. The intact perineurial cells, all perineuriomas, neurofibromas, cMPNSTs, spindle cell carcinomas and epithelial components of the complex carcinomas, all hemangiopericytomas and myo-pericytomas showed claudin-1 positivity. The schwannomas and other spindle shape cell tumours were negative for claudin-1.
Our findings suggest that an antibody against claudin-1, in combination with other antibodies, can be used as a novel diagnostic tool to differentiate canine peripheral nerve sheath tumours from other fusocellular tumours, and anti-claudin-1, together with other antibodies, can also be used to subclassify cBPNSTs. Furthermore, analysis of claudin-1 expression can help to differentiate between subgroups of canine perivascular wall tumours.
周围神经鞘瘤由肿瘤性施万细胞或周围神经鞘细胞组成，或由施万细胞、周围神经鞘细胞和成纤维细胞混合组成。本研究的首要目的是描述犬正常周围神经、犬良性周围神经鞘肿瘤（cBPNST），如神经鞘瘤、神经纤维瘤、周围神经鞘瘤和犬恶性周围神经鞘肿瘤（cMPNST）以及不同的其他良性和恶性犬梭形细胞肿瘤中紧密连接蛋白 Claudin-1 的表达情况。本研究的第二个目的是检查 Claudin-1 是否有助于区分犬血管周壁肿瘤的亚组。
活检和尸检样本（n=203）包括 10 个正常周围神经、20 个 cBPNST（4 个神经鞘瘤、8 个神经纤维瘤、8 个周围神经鞘瘤）、16 个 cMPNST、6 个砂粒体脑膜瘤、6 个皮肤纤维瘤、6 个平滑肌瘤、6 个黏液瘤、4 个梭形细胞血管瘤、2 个梭形细胞脂肪瘤、6 个纤维组织细胞瘤、8 个纤维肉瘤、8 个平滑肌肉瘤、6 个黏液肉瘤、8 个血管肉瘤、8 个间变性肉瘤、8 个无黑色素性梭形细胞黑色素瘤、8 个组织细胞肉瘤、8 个梭形细胞癌、8 个肌上皮瘤、8 个复合癌、5 个心脏横纹肌肉瘤、4 个滑膜肉瘤、5 个骨肉瘤、4 个软骨肉瘤和 4 个脂肪肉瘤；31 个犬血管周壁肿瘤：10 个血管外皮细胞瘤、8 个肌周细胞瘤、6 个血管平滑肌脂肪瘤、4 个血管平滑肌肉瘤、3 个血管纤维瘤。免疫组织化学试剂盒包括人源化抗体：抗 Claudin-1、神经元特异性烯醇化酶、S-100 蛋白、α-平滑肌肌动蛋白、波形蛋白、细胞角蛋白 AE1-AE3、Claudin-5、黑素瘤-A 和重钙调蛋白、钙调蛋白和结蛋白。完整的周围神经鞘细胞、所有的周围神经鞘瘤、神经纤维瘤、cMPNST、梭形细胞癌和复合癌的上皮成分、所有的血管外皮细胞瘤和肌周细胞瘤均为 Claudin-1 阳性。神经鞘瘤和其他梭形细胞肿瘤为 Claudin-1 阴性。
我们的研究结果表明，针对 Claudin-1 的抗体与其他抗体联合使用，可作为一种新的诊断工具，用于区分犬外周神经鞘肿瘤与其他梭形细胞肿瘤，并且 Claudin-1 与其他抗体联合使用也可用于对 cBPNST 进行亚分类。此外，Claudin-1 表达分析有助于区分犬血管周壁肿瘤的亚组。
