DOG1, discovered on GIST-1),TMEM16A, gene FLJ10261, TMEM16A,and ORAOV2 (overexpressed in oral carcinoma)

DOG1 is a protein of unknown function which is selectively expressed in gastrointestinal stromal tumour. The DNA sequence of DOG1 predicts eight transmembrane regions, suggesting that the protein may act as an ion channe and it has been identified wit. a calcium dependent,receptor-activated chloride channel protein, also known as anoctamin 1.  The gene is located at 11q13. DOG1.1 and DOG1.3 are both mouse monoclonal antibodies against the DOG1 protein.

Immunohistochemical expression

 

The following tissues do NOT stain for DOG-1:

 

  Gastrointestinal Stromal Tumour

c-KIT

 
positive negative total
DOG1 clone K9 positive 9604 264 9864
negative 274 274 544
total 9874 534 10404

GISTs by site:

  Reference 4

DOG clone K9

c-kit

 
0 + ++ +++ 0 + ++ +++
Oesophagus                
Stomach spindle cell sclerosing 2/36 1/36   33/36 1/36   3/36 33/36
spindle cell palisading vacuolated   1/116 2/116 113/116        
spindle cell hypercellular 3/47   1/47 43/47 2/47 1/47 1/47 43/47
spindle cell sarcomatous 3/68 1/68 2/68 62/68 3/68 2/68 6/68 57/68
epithelioid sclerosing 11/115 6/115 8/115 90/115 13/115 10/115 22/115 70/115
epithelioid discohesive 4/44 5/44 14/44 21/44 11/44 7/44 9/44 17/44
epithelioid hypercellular 2/31 1/31 2/31 26/31 4/31 1/31 3/31 23/31
epithelioid sarcomatous     1/9 8/9   1/9   8/9
epithelioid/spindle and mixed 5/71 2/71 5/71 59/71 6/71 2/71 12/71 51/71
total   17/537 37/537 445/537   24/537 60/537 413/537
Small intestine 14/372   6/372 352/372 9/372   3/372 360/372
Duodenum 4/57     53/57     1/57 56/57
Colon and rectum 5/64     59/64 4/64 1/64 4/64 55/64
Omentum 4/38     34/38 1/38 2/38 2/38 33/38
Abdomen NOS 7/90 1/90 3/90 79/90 8/90 3/90 8/90 71/90
Gastric paediatric 1/12     11/12 4/12     8/12
duodenal/small intestinal associated with neurofibromatosis       16/16       16/16
Total 65/1168 18/1168 45/1168 1040/1168 62/1168 30/1168 78/1168 998/1168
 

 

   

polyclonal anti-DOG1

DOG1.1

DOG1.3

K9

CD117

CD34

 

GIST

KIT-mutation positive GIST

 

200/2181, 23/252

197/2231

 

180/2211

142/2241

PDGFRA-mutation positive GIST

 

23/291, 2/112

12/291

 

3/321

9/331

Wild-type GIST

 

33/371, 4/72

31/371

 

29/351

20/381

CD117 positive GIST

 

26/262

 

 

 

 

CD117 negative GIST

 

10/282

 

 

 

 

GIST associated with neurofibromatosis

 

16/162

 

 

 

 

paediatric GIST

 

9/112

 

 

 

 

total

136/1393

370/4251

 

 

317/4281

254/4301

Leiomyoma

 

0/221

 

 

0/211

0/221

Leiomyoma, intramural, in the GI-tract

 

 

 

0/254

 

 

Leiomyoma, of muscularis mucosae of colon/rectum

 

 

 

0/94

 

 

Leiomyoma, uterine type, abdomen and retroperitoneum

 

 

 

5/424

 

 

Leiomyomatosis peritonealis disseminata

 

 

 

4/174

 

 

Leiomyosarcoma

 1/403

1/3261

 

0/684

3/3311

5/3341

Solitary fibrous tumour

 

 

 

0/84

 

 

Undifferentiated sarcoma

 

0/791

 

0/264

1/871

9/851

MPNST

 

0/851

 

0/84

0/861

11/831

Neurofibroma

 

0/531

 

 

0/551

38/551

Schwannoma

0/33

 

 

0/334

 

 

Glomus tumour

 

 

 

0/144

 

 

Synovial sarcoma

1/203

1/391

 

6/374  

0/441

1/441

Desmoid fibromatosis

0/173

0/351

 

0/204

0/321

0/311

Solitary fibrous tumour

 

0/201

 

 

0/211

12/201

DFSP

 

0/201

 

 

0/201

15/171

Dedifferentiated liposarcoma

 

0/91

 

0/184

0/101

3/81

Melanoma, metastatic to GI-tract

 

 

 

0/674

 

 

Desmoplastic melanoma

 

1/101

 

 

1/101

1/101

Inflammatory pseudotumour

 

0/41

 

 

0/51

0/51

Angiosarcoma

 

0/141

 

 

1/111

7/111

Osteosarcoma

 

0/141

 

 

0/141

0/141

Endometrial stromal sarcoma

 

0/131

 

 

0/121

0/131

Rhabdomyosarcoma

 

0/121

 

 

0/131

0/131

Epithelioid haemangioendothelioma

 

0/121

 

 

3/121

4/121

Well-differentiated liposarcoma

 

0/111

 

 

0/91

0/81

Extraskeletal myxoid chondrosarcoma

 

0/111

 

 

6/111

0/111

Low-grade fibromyxoid sarcoma

 

0/111

 

 

0/111

0/111

Fibroadenoma

 

0/111

 

 

0/111

9/111

Myxoid liposarcoma

 

0/101

 

 

0/101

0/91

Ewing/PNET

 1/93

0/101

 

0/114

1/101

0/91

Clear cell sarcoma

 

0/71

 

 

1/71

0/71

DSRCT

 

0/61

 

0/74

1/71

0/71

Pleomorphic liposarcoma

 

0/31

 

 

0/31

0/31

Epithelioid sarcoma

 

0/31

 

 

0/31

1/31

Fibrosarcoma

 1/43

0/31

 

 

0/31

0/31

Chondrosarcoma

 

0/31

 

 

0/31

0/31

PEComa, abdominal

 

 

 

0/34

 

 

Alveolar soft part sarcoma

 

0/21

 

 

2/21

0/21

Endometrial stromal sarcoma

 

 

 

0/84

 

 

Phyllodes tumour

 

0/21

 

 

0/21

0/21

Total for all sarcomas other than GISTs

 

3/9351

 

Hepatocellular carcinoma

 

1/41

 

Supplementary data on staining of non-sarcomatous tumours is available on line (subscription required)

Salivary gland

Basal cell adenoma

 

1/11

Adenoid cystic carcinoma

 

1/71

Pulmonary adenocarcinoma

 

1/81

Gastric adenocarcinoma, intestinal type

 

 

 

8/294

 

 

Gastric adenocarcinoma, signet ring cell-type/diffuse

 

 

 

3/134

 

 

Colonic adenocarcinoma

 

 

 

1/204

 

 

Squamous cell carcinoma of oesophagus

 

 

 

9/154

 

 

Undifferentiated sarcomatoid carcinoma of small intestine

 

 

 

0/214

 

 

Cholangiocarcinoma of liver

 

 

 

1/64

 

 

Carcinoid, small intestine

 

 

 

0/64

 

 

Extramedullary myeloid tumour, soft tissues, and skin

 

 

 

0/54

 

 

Inflammatory fibroid polyp, small intestine

 

 

 

0/654

 

 

Inflammatory myofibroblastic tumour, GI-tract

 

 

 

0/154

 

 

Kaposi sarcoma, soft tissue, and skin

 

 

 

0/194

 

 

Mastocytoma, skin

 

 

 

0/34

 

 

Neuroblastoma

 

 

 

0/74

 

 

Seminoma, testicular

 

 

 

0/164

 

 

Total for all tumours other than GIST

4/4603

 

 

5/5624

 

 

             

Diagnostic utility

References

1 Espinosa I, Lee CH, Kim MK, et al. A novel monoclonal antibody against DOG1 is a sensitive and specific marker for gastrointestinal stromal tumors. Am J Surg Pathol 2008; 32:210-8 Further information available on line

2 Liegl B, Hornick JL, Corless CL, et al. Monoclonal antibody DOG1.1 shows higher sensitivity than KIT in the diagnosis of gastrointestinal stromal tumors, including unusual subtypes. Am J Surg Pathol 2009; 33:437-46

3 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; 165:107-13 FULL TEXT

4 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.

This page last revised 1.10.2009.

©SMUHT/PW Bishop