Identification and characterization of primary cilia-positive salivary gland tumours exhibiting basaloid/myoepithelial differentiation
Identification and characterization of primary cilia-positive salivary gland tumours exhibiting basaloid/myoepithelial differentiation
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DOI：
10.1002/path.5688
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发表时间：
2021-05-29
影响因子：
7.3
通讯作者：
Sugimura, Haruhiko
中科院分区：
文献类型：
--
作者：
Shinmura, Kazuya;Kusafuka, Kimihide;Sugimura, Haruhiko
初级纤毛(PC)是细胞表面的非运动性触角状结构。许多类型的肿瘤显示PC丢失，而在某些肿瘤中PC被保留并参与肿瘤的发生。为了阐明主要唾液腺肿瘤(SGT)的PC状态和特征，我们通过免疫组织化学分析检测了100个主要SGT，包括8种组织病理学类型。多形性腺瘤(PA)、基底细胞腺瘤(BCA)、腺样囊性癌(AdCCs)和基底细胞腺癌(BCAcs)中PC均阳性(100%)，而Warthing瘤、涎腺导管癌、粘液表皮样癌和腺泡细胞癌中PC均为阴性(0%)。用纳米套管法对PC进行电子显微镜分析。值得注意的是，前一类肿瘤和后一类肿瘤分别含有和不含有基底样/肌上皮分化成分。4种PC阳性SGT的PC均较正常明显延长，并在导管和基底样/肿瘤性肌上皮成分中呈现PC特有的分布模式。2例PC阳性癌(ADCC和BCAc)的复发/转移部位仍有PC。有趣的是，Hedgehog信号通路的激活，主要表现为核GLI1的表达，在PC阳性的SGT中明显更频繁地被观察到。最后，我们鉴定了tau微管蛋白激酶2(TTBK2)可能参与了SGT中PC的产生。综上所述，我们的研究结果表明，具有基底/肌上皮分化(PA、BCA、ADCC和BCAc)的SGT是纤毛的，其PC具有肿瘤特异性特征，参与Hedgehog途径的激活，并与TTBK2上调有关，在SGT肿瘤发生和PC之间提供了重要的联系。(C)2021年大不列颠及爱尔兰病理学会。作者：John Wiley&Sons，Ltd.
Primary cilia (PC) are non-motile, antenna-like structures on the cell surface. Many types of neoplasms exhibit PC loss, whereas in some neoplasms PC are retained and involved in tumourigenesis. To elucidate the PC status and characteristics of major salivary gland tumours (SGTs), we examined 100 major SGTs encompassing eight histopathological types by immunohistochemical analysis. PC were present in all (100%) of the pleomorphic adenomas (PAs), basal cell adenomas (BCAs), adenoid cystic carcinomas (AdCCs), and basal cell adenocarcinomas (BCAcs) examined, but absent in all (0%) of the Warthin tumours, salivary duct carcinomas, mucoepidermoid carcinomas, and acinic cell carcinomas examined. PC were also detected by electron-microscopic analysis using the NanoSuit method. It is worthy of note that the former category and latter category of tumours contained and did not contain a basaloid/myoepithelial differentiation component, respectively. The four types of PC-positive SGTs showed longer PC than normal and exhibited a characteristic distribution pattern of the PC in the ductal and basaloid/neoplastic myoepithelial components. Two PC-positive carcinomas (AdCC and BCAc) still possessed PC in their recurrent/metastatic sites. Interestingly, activation of the Hedgehog signalling pathway, shown by predominantly nuclear GLI1 expression, was significantly more frequently observed in PC-positive SGTs. Finally, we identified tau tubulin kinase 2 (TTBK2) as being possibly involved in the production of PC in SGTs. Taken together, our findings indicate that SGTs that exhibit basaloid/myoepithelial differentiation (PA, BCA, AdCC, and BCAc) are ciliated, and their PC exhibit tumour-specific characteristics, are involved in activation of the Hedgehog pathway, and are associated with TTBK2 upregulation, providing a significant and important link between SGT tumourigenesis and PC. (c) 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.