Department of Pathology, Taihe Hospital, Hubei University of Medicine, Hubei, China 442000.
Department of Neurosurgery, Taihe Hospital, Hubei University of Medicine, Hubei, China 442000.
Hum Pathol. 2018 Jan;71:84-90. doi: 10.1016/j.humpath.2017.10.025. Epub 2017 Dec 5.
Aberrant expression of thyroid transcription factor-1 (TTF-1) has been observed in tumors arising in locations other than thyroid gland, lung and ventral forebrain. However, TTF-1 expression in schwannomas has not yet been studied. Meanwhile, a few inconsistent changes in protein expression have been identified between schwannomas and other peripheral nerve sheath tumors. We evaluated TTF-1 expression in 161 schwannomas and 43 other peripheral nervous system lesions, including ganglioneuromas (n = 8), malignant peripheral nerve sheath tumors (MPNSTs) (n = 11), neurofibromas (n = 24), and traumatic neuromas (n = 9), using immunohistochemistry and verified it using quantitative real-time reverse-transcription polymerase chain reaction (qPCR) to explore TTF-1 expression in peripheral nervous system lesions. Formalin-fixed paraffin-embedded (FFPE) tissues were obtained for both analyses. In this study, we observed nuclear TTF-1 staining in 109 (67.7%) schwannomas, including 102 of 131 (77.9%) conventional, 1 of 20 (5.0%) cellular and 6 of 10 (60.0%) plexiform schwannomas. Nuclear staining was not observed in normal peripheral nerves and non-schwannoma lesions. qPCR verified the aberrant expression and revealed a correlation between TTF-1 protein and mRNA levels (r = 0.633, P = .003). In conclusion, the data from our study show that TTF-1 is selectively expressed in the majority of schwannomas, particularly the conventional variants. Based on this observation, the TTF-1 protein and mRNA are specifically expressed in schwannomas. This highly aberrant expression of varying amounts of TTF-1 may provide new clues to reveal the pathogenesis of schwannoma.
甲状腺转录因子-1(TTF-1)的异常表达已在甲状腺、肺和前脑腹侧以外的部位发生的肿瘤中观察到。然而,神经鞘瘤中的 TTF-1 表达尚未得到研究。同时,神经鞘瘤和其他周围神经鞘肿瘤之间的蛋白表达也存在一些不一致的变化。我们使用免疫组织化学法评估了 161 例神经鞘瘤和 43 例其他周围神经系统病变中的 TTF-1 表达,包括神经节细胞瘤(n = 8)、恶性外周神经鞘肿瘤(MPNST)(n = 11)、神经纤维瘤(n = 24)和外伤性神经瘤(n = 9),并用定量实时逆转录聚合酶链反应(qPCR)进行验证,以探讨 TTF-1 在周围神经系统病变中的表达。这两项分析均使用福尔马林固定石蜡包埋(FFPE)组织进行。在这项研究中,我们观察到 109 例(67.7%)神经鞘瘤中有核 TTF-1 染色,包括 131 例常规神经鞘瘤中的 102 例(77.9%)、20 例细胞性神经鞘瘤中的 1 例(5.0%)和 10 例丛状神经鞘瘤中的 6 例(60.0%)。正常周围神经和非神经鞘瘤病变中未见核染色。qPCR 验证了异常表达,并显示 TTF-1 蛋白和 mRNA 水平之间存在相关性(r = 0.633,P =.003)。总之,我们的研究数据表明,TTF-1 选择性地表达在大多数神经鞘瘤中,尤其是常规型神经鞘瘤。基于这一观察结果,TTF-1 蛋白和 mRNA 特异性地表达在神经鞘瘤中。TTF-1 表达量的这种高度异常可能为揭示神经鞘瘤的发病机制提供新的线索。