DOG1 utility in diagnosing gastrointestinal stromal tumors on fine-needle aspiration

Background: Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal (GI) tract, and the majority contain KIT or PDGFRA activating mutations. Fine-needle aspiration biopsy (FNAB) is a valuable technique in the diagnosis of GIST and may allow for preoperative therapy with tyrosine kinase inhibitors (TKI). Because of the morphologic diversity of these tumors, routine diagnosis of GIST often relies on C-Kit immunohistochemical staining in addition to morphologic findings. However, up to 15% of GISTs are C-Kit negative. Antibodies with increased sensitivity and specificity for detection of C-Kit-negative GIST cases may be of value, especially because some of these cases may also benefit from TKI therapy.

Methods: Immunohistochemical staining for DOG-1, C-Kit (CD117) and protein kinase C theta (PKCθ) was performed on FNA cell-block preparations representing 30 GISTs, 17 leiomyosarcomas, 16 melanomas, 16 schwannomas, 11 adenoid cystic carcinomas, and 8 leiomyomas.

Results: DOG-1 was found to have 100% sensitivity and 100% specificity in diagnosis of GIST. C-Kit demonstrated 70% sensitivity and 76% specificity, and PKCθ showed 40% sensitivity and 86% specificity. When only spindle-cell neoplasms were considered (adenoid cystic carcinomas excluded), the specificity of C-Kit increased to 89%. Of interest, all C-Kit-negative cases showed DOG-1 positivity.

Conclusions: DOG-1 was the most sensitive and specific of the 3 markers for the diagnosis of GIST in cell-block preparations and may be of particular use in the diagnosis of C-Kit-negative GIST.