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Parallelism of DOG1 expression with recurrence risk in gastrointestinal stromal tumors bearing KIT or PDGFRA
Francesca Maria Rizzo1, Raffaele Palmirotta2,3, Andrea Marzullo4
1Department of Biomedical Sciences and Human Oncology, University of Bari "A. Moro", Piazza Giulio Cesare, 11-70124, Bari, Italy. frarizzo3@libero.it.
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.
Insights
DOG1 expression in gastrointestinal stromal tumors (GISTs) may predict patient prognosis. Strong DOG1 staining correlated with a worse recurrence-free survival rate, suggesting its use in risk stratification for GIST patients.
Area of Science:
- Oncology
- Gastrointestinal Pathology
Background:
- Gastrointestinal stromal tumors (GISTs) are driven by KIT or PDGFRA mutations, targeted by tyrosine kinase inhibitors (TKIs).
- Despite initial TKI response, most GISTs eventually progress, necessitating novel therapeutic approaches.
- DOG1 (discovered on GIST-1) is a sensitive diagnostic marker for GISTs, but its prognostic significance remains underexplored.
Purpose of the Study:
- To investigate the prognostic role of DOG1 expression in GISTs.
- To correlate DOG1 levels with clinical, pathological, and mutational features of GISTs.
- To assess the relationship between DOG1 expression and patient recurrence-free survival (RFS).
Main Methods:
- Immunohistochemistry (IHC) was used to evaluate DOG1 expression in 59 GIST patient samples.
- DOG1 levels were correlated with clinical and pathological characteristics and mutational status.
- Kaplan-Meier analysis assessed the association between DOG1 staining scores and RFS.
Main Results:
- DOG1 was expressed in 66% of CD117-positive GISTs.
- Strong DOG1 expression was associated with larger tumor size and wild-type molecular status.
- Kaplan-Meier analysis revealed that high DOG1 expression correlated with a poorer 2-year RFS rate.
Conclusions:
- DOG1 expression has a significant prognostic role in GISTs.
- High DOG1 expression may indicate a poor prognosis for GIST patients.
- DOG1 could be incorporated into risk stratification criteria for GIST management.
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