Parallelism of DOG1 expression with recurrence risk in gastrointestinal stromal tumors bearing KIT or PDGFRA mutations.

ABSTRACT

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are characterized by mutations of KIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) or PDGFRA (platelet-derived growth factor receptor α) that may be efficiently targeted by tyrosine kinase inhibitors (TKI). Notwithstanding the early responsiveness to TKI, the majority of GISTs progress, imposing the need for alternative therapeutic strategies. DOG1 (discovered on GIST-1) shows a higher sensitivity as a diagnostic marker than KIT, however its prognostic role has been little investigated. METHODS: We evaluated DOG1 expression by immunohistochemistry (IHC) in 59 patients with GISTs, and correlated its levels with clinical and pathological features as well as mutational status. Kaplan-Meier analysis was also applied to assess correlations of the staining score with patient recurrence-free survival (RFS). RESULTS: DOG1 was expressed in 66% of CD117(+) GISTs and highly associated with tumor size and the rate of wild-type tumors. Kaplan-Meier survival analysis showed that a strong DOG1 expression demonstrated by IHC correlated with a worse 2-year RFS rate, suggesting its potential ability to predict GISTs with poor prognosis. CONCLUSIONS: These findings suggest a prognostic role for DOG1, as well as its potential for inclusion in the criteria for risk stratification.