title: Distinct patterns of primary and motile cilia in Rathke's cleft cysts and craniopharyngioma subtypes.
abstract: Cilia are highly conserved organelles, which serve critical roles in development and physiology. Motile cilia are expressed in a limited range of tissues, where they principally regulate local extracellular fluid dynamics. In contrast, primary cilia are expressed by many vertebrate cell types during interphase, and are intimately involved in the cell cycle and signal transduction. Notably, primary cilia are essential for vertebrate hedgehog pathway activity. Improved detection of motile cilia may assist in the diagnosis of some pathologic entities such as Rathke's cleft cysts, whereas characterizing primary cilia in neoplastic tissues may implicate cilia-dependent signaling pathways as critical for tumorigenesis. We show that immunohistochemistry for the nuclear transcription factor FOXJ1, a master regulator of motile ciliogenesis, robustly labels the motile ciliated epithelium of Rathke's cleft cysts. FOXJ1 expression discriminates Rathke's cleft cysts from entities in the sellar/suprasellar region with overlapping histologic features such as craniopharyngiomas. Co-immunohistochemistry for FOXJ1 and markers that highlight motile cilia such as acetylated tubulin (TUBA4A) and the small GTPase ARL13B further enhance the ability to identify diagnostic epithelial cells. In addition to highlighting motile cilia, ARL13B immunohistochemistry also robustly highlights primary cilia in formalin-fixed paraffin-embedded sections. Primary cilia are present throughout the neoplastic epithelium of adamantinomatous craniopharyngioma, but are limited to basally oriented cells near the fibrovascular stroma in papillary craniopharyngioma. Consistent with this differing pattern of primary ciliation, adamantinomatous craniopharyngiomas express significantly higher levels of SHH, and downstream targets such as PTCH1 and GLI2, compared with papillary craniopharyngiomas. In conclusion, motile ciliated epithelium can be readily identified using immunohistochemistry for FOXJ1, TUBA4A, and ARL13B, facilitating the diagnosis of Rathke's cleft cysts. Primary cilia can be identified by ARL13B immunohistochemistry in routine pathology specimens. The widespread presence of primary cilia in adamantinomatous craniopharyngioma implicates cilia-dependent hedgehog signaling in the pathogenesis of adamantinomatous craniopharyngioma.
authors: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors: Shannon
authors: S
authors: Coy
authors: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors: Ziming
authors: Z
authors: Du
authors: Department of Pathology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
authors: Shu-Hsien
authors: SH
authors: Sheu
authors: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors: Terri
authors: T
authors: Woo
authors: Department of Pathology, Johns Hopkins University, Baltimore, MD, USA.
authors: Fausto J
authors: FJ
authors: Rodriguez
authors: Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
authors: Mark W
authors: MW
authors: Kieran
authors: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.|Department of Pathology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.|Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.|Ludwig Center at Harvard, Harvard Medical School, Boston, MA, USA.
authors: Sandro
authors: S
authors: Santagata
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D020863:Central Nervous System Cysts / Q000473:pathology*; D002648:Child; D002923:Cilia / Q000473:pathology*; D003397:Craniopharyngioma / Q000473:pathology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis / Q000096:biosynthesis; D006801:Humans; D008297:Male; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000473:pathology*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C106349:FOXJ1 protein, human; D051858:Forkhead Transcription Factors