Contribution of DOG1 expression to the diagnosis of gastrointestinal stromal tumors

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract, and the majority contain KIT or PDGFRA-activating mutations. However, up to 10% of GISTs are c-kit-negative. Antibodies with increased sensitivity and specificity for the detection of c-kit-negative GIST cases may be of value, especially because some of these cases may also benefit from tyrosine kinase inhibitor therapy. Hematoxylin and Eosin sections of 33 GISTs were re-examined in order to define histopathological criteria used in risk assessment of these tumors. Immunohistochemistry with a panel of antibodies [c-kit, DOG1 (discovered on GIST 1), CD34, smooth muscle actin (SMA), Desmin, S100 and Ki67] was performed on 5μm-thick paraffin sections of all tumors. Statistical analysis of immunohistochemical studies showed that DOG1 and CD117 were the most sensitive and specific antibodies in the diagnosis of GISTs. Other antibodies were unhelpful in confirming a diagnosis of GIST, but were particularly useful in the differential diagnosis. Reactivity for DOG1 may aid in the diagnosis of GISTs, which fail to express c-kit antigen, and lead to appropriate treatment with imatinib mesylate, an inhibitor of the KIT tyrosine kinase.