DOG1: A Novel Marker of Salivary Acinar Differentiation.
Jacinthe Chenevert, Umamaheswar Duvvuri, Jean H Kim, Raja R Seethala. University of Pittsburgh Medical Center, PA
Background: DOG1 (TMEM16A) is a calcium-activated chlorine channel expressed in a variety of normal and tumor tissues, most notably gastrointestinal stromal tumors. In murine models, DOG1 is highly expressed in salivary gland acini and noted to be critical for saliva secretion. We herein validate this finding in human salivary tissues and describe its distribution in normal salivary tissues and tumors.
Design: TMEM16A mRNA levels were evaluated by quantitative RT-PCR in 10 normal parotid and 10 normal squamous epithelial frozen tissue samples. Immunohistochemical staining for DOG1 (Clone 1.1, Zeta Co, Sierra Madre, CA, dilution: 1:50) was then performed on paraffin sections from 30 parotid tumors (25 with adjacent normal) as well as 3 submandibular sialadenitis cases and one sinonasal mucoserous gland biopsy. Tumors consisted of 18 acinic cell carcinomas (AciCC) and 12 non AciCC (6 salivary duct carcinomas, 4 pleomorphic adenomas, 1 Warthin tumor, and 1 sebaceous lymphadenoma). Immunohistochemical parameters evaluated included: cell type distribution, % of cells, intensity (scale: 0-3) and subcellular localization.
Results: TMEM16A mRNA levels were significantly higher (5-fold increase, p<0.05) in normal parotid tissue as compared to squamous epithelium. Immunohistochemical evaluation for DOG1 demonstrated diffuse 2+ apical (luminal) staining in normal serous acini in all non neoplastic salivary tissue types, 1+ apical staining in mucous acini, and very focal 1+ staining of intercalated ducts. Myoepithelial cells, striated and excretory ducts were all invariably negative. In tumors, DOG1 staining was almost entirely restricted to AciCC. All 18 cases contained 3+ apical staining with 16 cases showing diffuse staining (100% of cells). Truly solid areas showed far less apical staining, while areas with mainly vacuolated cells had only focal 1-2+ staining compared to other cell types in AciCC. 15/18 cases showed cytoplasmic staining 1-2+ and 10/18 cases showed membranous staining 1-2+. All the non-AciCC tested so far are largely negative, though 1+ apical staining was noted in scattered ducts of pleomorphic adenoma.
Conclusions: DOG1 is highly expressed in human salivary acini. It is retained in AciCC and can potentially serve as a marker of acinar differentiation. A preliminary survey of non-AciCC supports the specificity of DOG1 though this must be validated.
Category: Head & Neck
Monday, February 28, 2011 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 158, Monday Morning