Parallelism of DOG1 expression with recurrence risk in gastrointestinal stromal tumors bearing KIT or PDGFRA mutationsReport as inadecuate




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BMC Cancer

, 16:87

Medical and radiation oncology

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.

KeywordsGastrointestinal stromal tumors DOG1 Size Mutation Prognostic value Risk AbbreviationsANO1anoctamin-1

DOG1discovered on GIST-1

FFPEformalin-fixed, paraffin-embedded

GISTsgastrointestinal stromal tumor

HPFshigh-power fields

IGFinsulin-like growth factor

IHCimmunohistochemistry

KITv-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog

OSoverall survival

PCRpolymerase chain reaction

PDGFRAplatelet-derived growth factor receptor, alpha polypeptide

Rbretinoblastoma

RFSrecurrence-free survival

SDHsuccinate dehydrogenase

TKItyrosine kinase inhibitors

TMEM16Atransmembrane member 16A

WTwild-type

Electronic supplementary materialThe online version of this article doi:10.1186-s12885-016-2111-x contains supplementary material, which is available to authorized users.

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Author: Francesca Maria Rizzo - Raffaele Palmirotta - Andrea Marzullo - Nicoletta Resta - Mauro Cives - Marco Tucci - Franco Silve

Source: https://link.springer.com/







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