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.

Fujiwara M, Kwok S, Yano H, Pai RK. Arginase-1 is a more sensitive marker of hepatic differentiation than HepPar-1 and glypican-3 in fine-needle aspiration biopsies. Cancer Cytopathol. 2012 Aug 25;120(4):230-7. doi: 10.2002/cncy.21190.Epub 2012 Mar 20. PubMed PMID: 22434791. He H, Fang W, Liu X, Weiss LM, Chu PG. Frequent expression of glypican-3 in Merkel cell carcinoma: an immunohistochemical study of 55 cases. Appl Immunohistochem Mol Morphol. 2009 Jan;17(1):40-6. doi: 10.1097/PAI.0b013e31817b67d1. PubMed PMID: 18813128. Kandil D, Leiman G, Allegretta M, Evans M. Glypican-3 protein expression in primary and metastatic melanoma: a combined immunohistochemistry and immunocytochemistry study. Cancer. 2009 Aug 25;117(4):271-8. doi:10.2002/cncy.20032. PubMed PMID: 19517479. Mounajjed T, Zhang L, Wu TT. Glypican-3 expression in gastrointestinal and pancreatic epithelial neoplasms. Hum Pathol. 2013 Apr;44(4):542-50. doi: 10.1016/j.humpath.2012.06.016. Epub 2012 Oct 15. PubMed PMID: 23079207. Preda O, Nicolae A, Aneiros-Fernández J, Borda A, Nogales FF. Glypican 3 is a sensitive, but not a specific, marker for the diagnosis of yolk sac tumours.Histopathology. 2011 Jan;58(2):312-4; author reply 314-5. doi:10.1111/j.1365-2559.2010.03735.x. Epub 2011 Jan 24. PubMed PMID: 21255065. Rabban JT, Zaloudek CJ. A practical approach to immunohistochemical diagnosis of ovarian germ cell tumours and sex cord-stromal tumours. Histopathology. 2013 Jan;62(1):71-88. doi: 10.1111/his.12052. Review. PubMed PMID: 23240671. Thway K, Selfe J, Missiaglia E, Fisher C, Shipley J. Glypican-3 is expressed in rhabdomyosarcomas but not adult spindle cell and pleomorphic sarcomas. J Clin Pathol. 2011 Jul;64(7):587-91. doi: 10.1136/jclinpath-2011-200071. Epub 2011 Apr 14. PubMed PMID: 21493758. Timek DT, Shi J, Liu H, Lin F. Arginase-1, HepPar-1, and Glypican-3 are the most effective panel of markers in distinguishing hepatocellular carcinoma from metastatic tumor on fine-needle aspiration specimens. Am J Clin Pathol. 2012 Aug;138(2):203-10. doi: 10.1309/AJCPK1ZC9WNHCCMU. PubMed PMID: 22904131. Trinh DT, Shibata K, Hirosawa T, Umezu T, Mizuno M, Kajiyama H, Kikkawa F.Diagnostic utility of CD117, CD133, SALL4, OCT4, TCL1 and glypican-3 in malignant germ cell tumors of the ovary. J Obstet Gynaecol Res. 2012 May;38(5):841-8. doi:10.1111/j.1447-0756.2011.01798.x. Epub 2012 Mar 26. PubMed PMID: 22448662. Zhang L, Liu H, Sun L, Li N, Ding H, Zheng J. Glypican-3 as a potential differential diagnosis marker for hepatocellular carcinoma: a tissue microarray-based study. Acta Histochem. 2012 Oct;114(6):547-52. doi:10.1016/j.acthis.2011.10.003. Epub 2011 Nov 26. PubMed PMID: 22119409.