title: DOG1: a novel marker of salivary acinar and intercalated duct differentiation.
abstract: Anoctamin-1 (ANO1) (DOG1, TMEM16a) is a calcium-activated chloride channel initially described in gastrointestinal stromal tumors, but now known to be expressed in a variety of normal and tumor tissues including salivary tissue in murine models. We herein perform a comprehensive survey of DOG1 expression in 156 cases containing non-neoplastic human salivary tissues and tumors. ANO1 mRNA levels were significantly higher (8-fold increase, P<0.0001) in normal parotid tissue (n=6) as compared with squamous mucosa (n=15). By immunohistochemistry, DOG1 showed a diffuse moderate (2+) apical membranous staining pattern in normal serous acini, 1+ apical membranous pattern in mucous acini, and variable 1-2+ apical staining of distal intercalated ducts. Myoepithelial cells, striated and excretory ducts were invariably negative. All acinic cell carcinomas (n=28) were DOG1 positive demonstrating a complex mixture of intense (3+) apical membranous, cytoplasmic and complete membranous staining. Most ductal tumor types were negative or only showed a subset of positive cases. Within the biphasic tumor category, adenoid cystic carcinomas (18/24 cases) and epithelial-myoepithelial carcinomas (8/15 cases) were frequently positive, often showing a distinctive combined apical ductal and membranous/cytoplasmic myoepithelial staining profile. Thus, DOG1 staining is a marker of salivary acinar and to a lesser extent intercalated duct differentiation. Strong staining can be used to support the diagnosis of acinic cell carcinoma. DOG1 may also be a marker of a 'transformed' myoepithelial phenotype in a subset of biphasic salivary gland malignancies.
authors.affiliation: Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Jacinthe
authors.initials: J
authors.lastname: Chênevert
authors.forename: Umamaheswar
authors.initials: U
authors.lastname: Duvvuri
authors.forename: Simion
authors.initials: S
authors.lastname: Chiosea
authors.forename: Sanja
authors.initials: S
authors.lastname: Dacic
authors.forename: Kathleen
authors.initials: K
authors.lastname: Cieply
authors.forename: Jean
authors.initials: J
authors.lastname: Kim
authors.forename: Daniel
authors.initials: D
authors.lastname: Shiwarski
authors.forename: Raja R
authors.initials: RR
authors.lastname: Seethala
mesh_terms: D061354:Acinar Cells / Q000378:metabolism / Q000473:pathology; D000075369:Anoctamin-1; D014408:Biomarkers, Tumor / Q000032:analysis*; D002277:Carcinoma / Q000378:metabolism / Q000473:pathology; D018267:Carcinoma, Acinar Cell / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D018118:Chloride Channels / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018987:Salivary Ducts / Q000378:metabolism* / Q000473:pathology; D012468:Salivary Gland Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: C476213:ANO1 protein, human; D000075369:Anoctamin-1; D014408:Biomarkers, Tumor; D018118:Chloride Channels; D009363:Neoplasm Proteins; D012333:RNA, Messenger