Identification and characterization of primary cilia‐positive salivary gland tumours exhibiting basaloid/myoepithelial differentiation. Issue 5 (29th May 2021)

• Record Type: Journal Article
• Authors: Shinmura, Kazuya; Kusafuka, Kimihide; Kawasaki, Hideya; Kato, Hisami; Hariyama, Takahiko; Tsuchiya, Kazuo; Kawanishi, Yuichi; Funai, Kazuhito; Misawa, Kiyoshi; Mineta, Hiroyuki; Sugimura, Haruhiko
• Is Part Of: Journal of pathology. Volume 254:Issue 5(2021)
• Page Start: 519
• Page End: 530
• Publication Date: 2021-05-29
• Subjects: adenoid cystic carcinoma -- ARL13B -- basal cell adenocarcinoma -- basal cell adenoma -- basaloid/myoepithelial differentiation -- Hedgehog signalling pathway -- primary cilia -- salivary gland tumour -- TTBK2; Pathology -- Periodicals; 616.07
• DOI: 10.1002/path.5688
• Languages: English
• ISSNs: 0022-3417

Abstract

Abstract: 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. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.