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

Francesca Maria Rizzo,Franco Silvestris,Marco Tucci,Nicoletta Resta,Raffaele Palmirotta,Mauro Cives,Andrea Marzullo

doi:10.1186/s12885-016-2111-x

Abstract

BackgroundGastrointestinal 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.MethodsWe 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).ResultsDOG1 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.ConclusionsThese findings suggest a prognostic role for DOG1, as well as its potential for inclusion in the criteria for risk stratification.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2111-x) contains supplementary material, which is available to authorized users.

Highlights

IntroductionGastrointestinal 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)
Gastrointestinal stromal tumors (GISTs) are characterized by mutations of KIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) or platelet-derived growth factor receptor (PDGFRA) that may be efficiently targeted by tyrosine kinase inhibitors (TKI)
Mutational status was available in 53 patients harboring mutations of KIT (n = 35; 66.1 %) and PDGFRA (n = 4; 7.5 %) (Fig. 1), whereas in 14 patients (26.4 %) both genes were WT

Summary

Introduction

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). Gastrointestinal stromal tumors (GISTs) develop within the digestive tract and harbor functional mutations of KIT (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) and PDGFRA (platelet-derived growth factor receptor-α) that primarily drive the tumor growth and progression [1, 2]. Rizzo et al BMC Cancer (2016) 16:87 characterization may be required, such as searching for germline or de novo mutations of SDH (succinate dehydrogenase) subunits located on the inner membrane of the mitochondria, or even mutations of the RAS-pathway [6] Among the latter, the frequency of BRAF mutations varies from 2 to 13 %, whereas KRAS mutations are extremely rare (

Methods

Results

Discussion

Conclusion