DOG1

Synonyms: anoctamin-1 (ANO1), FLJ10261, ORAOV2, TMEM16A. Nature: Cell membrane calcium activated chloride channel protein encoded by a gene in the CCND1-EMS1 locus on Chr 11q13. Function and occurrence: DOG1 is detected in gastrointestinal Cajal cells, acinic cells in salivary glands (apical membraneous staining, particularly in serous cells), pancreatic centroacinar cells, liver cells, and epithelium of biliary tract, breast, stomach, and prostate.

+: >90% positive, +/-: 50-90% positive, -/+: 10 - >50% positive, -(+): 1-<10% positive, -: <1% positive, ?: conflicting evidence or insufficient information. + More than 90% of all gastrointestinal stromal tumours (GISTs) are DOG1 positive, irrespective of kit mutation and CD117 positivity. The staining pattern varies from cytoplasmic to membranous, with usually strong, diffuse intensity. DOG1 is also detected in almost all cases of salivary acinic cell carcinoma, pancreatic solid-pseudopapillary tumor, chromophobic renal cell carcinoma, and renal oncocytoma. Abdominal synovial sarcoma has shown positivity in 4/4 cases. +/- DOG1 is detected in the majority of cases of salivary adenoid cystic carcinoma, esophageal adenocarcinoma and squamous cell carcinoma, and chondroblastoma. -/+ & -(+) DOG1 is demonstrated less frequently or rarely in a large number of carcinoma types derived from lung, liver, salivary glands, stomach and intestine, and in uterine leiomyosarcoma. - DOG1 has been detected in rare cases of synovial sarcoma, non-uterine leiomyosarcoma, fibrosarcoma and Ewing sarcoma. Other sarcomas are virtually always negative. Clear cell renal cell carcinoma is negative. ? Conflicting information is published about the occurrence of DOG1 in seminoma. There are few reports on DOG1 expression in carcinomas and malignant melanoma.

DOG1 is an important marker in the identification of GIST together with CD117, slightly more sensitive (particularly in gastric GIST without c-kit mutation) and also more specific than CD117. DOG1 is also useful in the classification of salivary carcinomas, and pancreatic and renal tumours as detailed above.

Appendix can be recommended as positive and negative tissue control for DOG1. A moderate to strong predominantly membranous staining reaction must be seen in virtually all Cajal cells, whereas a weak staining reaction must be seen in basal columnar epithelial cells, scattered endothelial and smooth muscle cells of vessels. No staining should be seen in mast cells and smooth muscle cells of muscularis propria and lamina muscularis mucosae.

Jansen K et al. DOG1 expression is common in human tumors: A tissue microarray study on more than 15,000 tissue samples. Pathol Res Pract. 2021 Dec;228:153663. doi: 10.1016/j.prp.2021.153663. Link

Miettinen M, Wang ZF, Lasota J. DOG1 antibody in the differential diagnosis of gastrointestinal stromal tumors: a study of 1840 cases. Am J Surg Pathol. 2009 Sep;33(9):1401-8. Link

Liegl B, Hornick JL, Corless CL, Fletcher CD. Monoclonal antibody DOG1.1 shows higher sensitivity than KIT in the diagnosis of gastrointestinal stromal tumors, including unusual subtypes. Am J Surg Pathol. 2009 Mar;33(3):437-46.Link