DOG1

Synonyms: Discovered on GIST 1, Anoctamin-1, ANO1, FLJ10261, ORAOV2, TMEM16A

by Jan Klos

Background

It is calcium activated, cell membrane protein involved in chloride channel.  Encoded by gene in the CCND1-EMS1 locus on Chr 11q13.

Staining in normal cells

Interstitial cells of Cajal, gastric epithelium, pancreatic centroacinar cells, pancreatic endocrine cells, and liver cells as well as epithelium of biliary tract, breast, stomach and prostate are positive.

Staining in tumors

Primary and metastatic GIST of different locations (often reported more sensitive than CD117 marker), pancreatic solid-pseudopapillary neoplasm, tumors of salivary glands (adenoid cystic carcinoma, low grade mucoepidermoid carcinoma, acinar cell carcinoma and low grade ductal adenocarcinoma), chromophobe renal cell carcinoma and renal oncocytoma. Positivity is also reported in ~40% squamous cell esophageal and ~ 30% of gastric adenocarcinomas (both intestinal and signet-ring type), glomus tumor, mammary analog secretory carcinoma (MASC). Lower number of cases (<20%) of cholangiocarcinoma,  Sertoli cell tumor, peritoneal leiomyomatosis, synovial sarcoma, fibrosarcoma, malignant melanoma, Ewing sarcoma, teratoma, colorectal adenocarcinoma, endometrial stromal sarcoma are also reported positive. Expression in squamous cell carcinoma of head and neck is inversely related to HPV status and correlates with worse prognosis.
Occasionally uterine type leiomyomas can be colonized by DOG1 positive Cajal cells and this colonization should not be confused with GIST!

Staining pattern

Staining pattern is mixed, usually strong and diffuse varying from membranous to cytoplasmic (often both).

Control tissue

Appendix

Application

  • DOG1 is an important, sensitive however not fully specific marker in the identification of GIST together with CD117. It is slightly more sensitive (particularly for gastric GIST without c-kit mutation) and seems to be more specific than CD117.
  • Recommended to use with CD117 as only 2,6% of GIST are negative for both markers.
  • DOG1 is also useful in the classification of salivary carcinomas, pancreatic and renal tumors. Variation in reported reactivity depending on antibody type and clones may be present.
  • Appropriate clinical and morphological context is as always essential for correct diagnosis!

Selected references

  1. Bergmann F, Andrulis M, Hartwig W, et al. Discovered on gastrointestinal stromal tumor 1 (DOG1) is expressed in pancreatic centroacinar cells and in solid-pseudopapillary neoplasms – novel evidence for a histogenetic relationship.  Hum Pathol. 2011 Jun;42(6):817-23. doi: 10.1016/j.humpath.2010.10.005. Epub 2011 Feb 4. 
  2. Dabbs DJ. Diagnostic Immunohistochemistry: Theranostic and Genomic Applications 5th edition 2018
  3. Hermida-Prado F1,2, Menéndez ST3,4, Albornoz-Afanasiev P5, et al. Distinctive Expression and Amplification of Genes at 11q13 in Relation to HPV Status with Impact on Survival in Head and Neck Cancer Patients. J Clin Med. 2018 Dec 1;7(12). pii: E501. doi: 10.3390/jcm7120501.
  4. https://app.immunoquery.com
  5. https://www.nordiqc.org/epitope.php?id=7
  6. Pernick N. DOG1. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/stainsdog1.html. Accessed May 12th, 2020.
  7. Miettinen M, Wang ZF, Lasota J. DOG1 antibody in the differential diagnosis of gastrointrestinal  stromal  tumors: a study of 1840 cases.  Am J Surg Pathol. 2009 Sep;33(9):1401-8.  doi:10.1097/PAS.0b013e3181a90e1a.
  8. Swalchick W, Shamekh R, Bui MM. Is DOG1 Immunoreactivity Specific to Gastrointestinal Stromal Tumor?  Cancer Control. 2015 Oct;22(4):498-504.
  9. West RB., Corless CL.,  Chen X., et al. The Novel Marker, DOG1, Is Expressed Ubiquitously in Gastrointestinal Stromal Tumors Irrespective of KIT or PDGFRA Mutation Status.  Am J Pathol. 2004 Jul; 165(1): 107–113.