Clinical and prognostic significance of Raf kinase inhibitory protein expression in gastrointestinal stromal tumors.

AIM: To detect the expression of Raf kinase inhibitory protein (RKIP) in gastrointestinal stromal tumors (GISTs) and to analyze its relationship with clinicopatholgical characteristics and prognosis of this disease.

METHODS: Sixty-three patients with pathologically diagnosed GISTs who underwent surgical resection at the Shengjing Hospital of China Medical University from January 2011 to January 2015 and had complete clinical, pathological, and follow-up data were included. Immunohistochemical method was used to detect the expression of RKIP in GIST tissue samples from these patients. Kaplan-Meier method was used to calculate the survival rate of 60 patients with complete follow-up data, and Cox regression analysis was performed to identify factors affecting the prognosis of patients GISTs to evaluate further the diagnostic and prognostic value of RKIP in GISTs.

RESULTS: In GIST tissues, RKIP positive signals, manifesting as brownish yellow or brown granules, were located in the cytoplasm or on the membrane. Of 63 tissue samples included in this study, 34 (54%) were positive and 29 (46%) were negative for RKIP expression. Statistical analysis showed that RKIP expression in GISTs was significantly associated with tumor size, National Institutes of Health (NIH) risk grade, and mucosal invasion, but had no significant association with age, gender, tumor location, or the number of mitotic figures. Univariate Kaplan-Meier analysis revealed that the 1-, 3-, and 5-year survival rates were 94.4%, 89.2%, and 80.5% for patients with positive RKIP expression, and 88.6%, 68.2%, and 48.2% for patients with negative RKIP expression, suggesting that patients with high RKIP expression had significantly higher survival rates than those with low expression (Log-rank test, P = 0.0015). Cox regression analysis demonstrated that NIH risk grade was significantly associated with the prognosis of GISTs ( P = 0.037), suggesting that NIH risk grade is a significant predictor of the prognosis of GISTs. RKIP expression had a tendency to predict the survival of GISTs ( P = 0.122), suggesting that RKIP expression may have appreciated value to predict the prognosis of GISTs.

CONCLUSION: This study demonstrated that: (1) RKIP expression in GISTs is associated with tumor size, NIH risk grade, and mucosal invasion, and low or no expression of RKIP predicts a high malignancy potential; (2) high RKIP correlates positively with the survival of patients with GISTs; and (3) RKIP expression has appreciated value for predicting the survival of patients with GISTs, although it is not an independent prognostic factor in GISTs.