DOG1: a novel marker of salivary acinar and intercalated duct differentiation

• DOI: 10.1038/modpathol.2012.57
• Publication Date: 2012-03-30T11:42:35Z
• Authors: Jacinthe Chênevert; Umamaheswar Duvvuri; Simion Chiosea; Sanja Dacic; Kathleen Cieply; Jean Kim; Daniel Shiwarski; Raja R Seethala
• Keywords: 0301 basic medicine; Carcinoma, Acinar Cell; Reverse Transcriptase Polymerase Chain Reaction; Carcinoma; Cell Differentiation; Acinar Cells; Salivary Gland Neoplasms; Immunohistochemistry; Neoplasm Proteins; 3. Good health; 03 medical and health sciences; Cell Transformation, Neoplastic; Chloride Channels; Biomarkers, Tumor; Humans; Salivary Ducts; RNA, Messenger; Anoctamin-1; In Situ Hybridization, Fluorescence

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.