[734] DOG-1 Expression in Detection of Gastrointestinal Stromal Tumors

AC Schmitt, C Cohen, MT Siddiqui. Emory University Hospital, Atlanta, GA

Background: Gastrointestinal stromal tumors (GIST) are characterized by KIT or PDGFRA activating mutations. The diagnosis of GIST relies on C-Kit immunohistochemical (IHC) detection; however up to 15% of GIST are C-Kit negative. Antibodies with increased sensitivity in the detection of C-kit negative GIST cases could be of value, as they might also benefit from imatinib mesylate therapy. Gene expression profiling studies have identified two novel proteins strongly expressed in GIST: DOG-1 and protein kinase C- theta (PKCθ), a signaling molecule important in T-cell activation. DOG-1 is a protein of unknown function highly expressed in GIST, irrespective of KIT or PDGFRA mutation status. Compared to C-Kit, it is rarely expressed in other soft tissue tumors. We investigated two DOG-1 antibody clones, to determine their use in the diagnosis of GIST, especially C-Kit negative GIST.
Design: IHC was performed on 40 GIST, 5 adenoid cystic carcinomas (ACC), 5 mastocytomas (MC), and 5 pure seminomas (SEM). The staining pattern of two DOG-1 mouse monoclonal antibody clones, (Cell Marque SP31 and Leica Microsystems K9); two C-Kit antibody clones, (DakoCytomation polyclonal antibody [pC-Kit], and Novocastra T595 monoclonal antibody [mC-Kit]); and BD Biosciences PKCθ monoclonal antibody was analyzed.
Results:

Total of positive staining cases.

	DOG-1 (SP31)	DOG-1 (K9)	pC-Kit	mC-Kit	PKCθ
GIST	38/40	36/40	28/40	22/40	23/40
ACC	0	0	5/5	5/5	0
MC	0	0	4/5	4/5	0
SEM	0	0	5/5	4/5	0

40 GIST cases studied, only one case negative for all 5 antibodies.

Sensitivity and Specificity of antibody panel used.

	DOG-1 (SP31)	DOG-1 (K9)	pC-Kit	mC-Kit	PKCθ
Sensitivity	0.95	0.90	0.70	0.55	0.57
Specificity	1.00	1.00	0.06	0.13	1.00

C-Kit Negative GIST included pC-Kit 12/40), mC-Kit (18/40) and both p and mC-Kit (11/40). Of the 11 totally negative cases, DOG-1 (SP3) was positive in 9/11(82%), DOG-1 (K9) was positive in 9/11 (82%) and both DOG-1 (SP31 and K) were positive in 10/11 (91%) of the cases.
Conclusions: Both DOG-1 (SP31 and K9) antibodies have a high sensitivity and specificity for diagnosis of GIST. They are also both more sensitive and specific for the diagnosis of GIST than C-Kit. PKCθ shows a lower sensitivity but an equal specificity to DOG-1. In summary, routine IHC detection of GIST with DOG-1 antibody can be very helpful, especially in C-Kit negative cases.
Category: Gastrointestinal

Monday, March 22, 2010 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 111, Monday Morning