*S100 15-20% in small intestine GIST, more frequent in NF1 associated cases
#Loss of SDHB staining identifies a distinct subset of syndromic or pediatric GIST
DOG1 (Discovered On GIST) is a newly available monoclonal antibody that appears to be more sensitive and specific than CD117
The percent positive depends on case selection
Consult cases tend to have lower reactivity
Cases from treatment series tend to have high KIT reactivity
See side by side comparison below
CD117 usually diffuse strong staining
Frequently perinuclear dots
Occasionally focal
In side by side comparison studies:
CD117
DOG1
GIST
74%
87%
GIST with PDGFRA mutation
9%
79%
Leiomyosarcoma
0.9%
0.3%
Synovial Sarcoma
0%
2.5%
Other lesions in DDx
0.5%
0.25%
Other sarcomas
10%
0%
Melanoma
30%
3%
Seminoma
86%
0%
Other non-mesenchymal
16%
1%
From Espinosa 2008
Low percentage reactivities due to referral bias
Non-reactive cases more often sent for consultation
DOG1 positive on 36-70% of KIT negative GIST (Liegl; Espinosa)
Miettinen 2009 reports 6/37 synovial sarcomas reactive for DOG1
Molecular Studies
Most have gain of function mutations in KIT
Actual percentage reported is highly variable, from 50-90%
May depend upon case selection or technical matters
From unselected or population based studies:
KIT 65-75%
PDGFRA 5-12%
In series of treated patients, KIT is frequently higher as it may be an inclusion criterion
In series of referral cases, KIT is frequently lower, as negative cases are more often referred
About 1/3 of KIT mutation negative cases have mutations in PDGFRA instead
Pediatric and NF1 associated GIST typically lack KIT and PDGFRA mutations
CD117 and DOG1 positive staining in nearly all cases
Various mutations can be correlated to response to specific therapies (see Lasota 2008)
