The role of the DOG1 antibody in the diagnosis of gastrointestinal stromal tumours - GIST

Abstract

Gatrointestinal stromal tumours (GIST) harbour oncogenic mutations in tyrosin kynases receptors (RTKs) including KIT and PDGFRA. The inhibition of this activity has been regarded as the primary target for the treatment of these patients. Diagnosis of GIST relies on c-KIT inmunoreactivity; however there is a 4-15% of GISTs that are C-KIT negative which may lead to underdiagnosis of GISTs and possible withholding of therapy. The novel gene DOG1 has been found overexpressed in GISTs and has potential as a diagnostic marker for GISTs showing even more sensitivity (Se) and specificity (Sp) than c-KIT for the diagnosis of these tumors. In this study we compared the (Se) and (Sp) of DOG1 in typical and atypical GISTs (c-KIT positive or negative) with c-KIT and other mesenchymal neoplasms in the differential diagnosis of GISTs We examined 40 GIST (39 showed inmunoreactivity for c-KIT and one was c-KIT negative) and another seven fusiform tumors. An inmunohistochemical panel was performed with c-KIT, CD34, smooth muscle actin, DOG1 and S100 antibodies on both types of neoplasms. The overall Se and Sp of DOG1 and KIT in GISTs were nearly identical: 100 and 97,5%. Negativity for DOG1 was observed in all fusiform mesenchymal neoplasms. DOG1 is highly expressed in GIST and its expression seems quite specific for these tumours when the differential diagnosis includes another mesenchymal neoplasms. DOG1 should be added to the diagnostic panel evaluating GISTs.