Clinical and Prognostic Significance of KIT exon 11 Mutation and Ki-67 Expression in Primary Gastrointestinal Stromal Tumor (GIST)

Abstract

Abstract Purpose Gastrointestinal stromal tumor (GIST) are rare and heterogeneous, and there are no large-scale clinical and prognostic analyses of different mutation types in KIT exon combined with Ki-67 levels, we aimed to explore the clinical feature and prognostic significance of different types of KIT exon 11 mutations combined with the different expression levels of Ki-67 in GIST. Methods In this research, 444 specimens of primary GISTs were collected from the largest single-center sample bank in China and genetically tested to confirm the mutations in KIT exon 11, and the expression of Ki-67 was determined by immunohistochemical methods. The pertinence between KIT exon 11 mutation, Ki-67 expression status, and clinicopathological features was analyzed using the chi-square test. Influencing factors of survival were evaluated by Kaplan–Meier analysis and the Log-Rank test was used to analyze differences between survival curves. Univariate and multivariate analyses were performed using the Cox regression model. The ROC curve was used to compare the NIH risk classification with the new risk classification that included ki-67 and exon 11 mutations. Results There is a significant correlation between mutation in KIT exon 11 and risk classification (P = 0.04), Mitotic figures (P = 0.049), and CD34 positivity (P = 0.033). Besides, the expression level of Ki-67 was significantly correlated with tumor diameter (P = 0.008), tumor shape (P = 0.017), risk classification (P < 0.0001), and Mitotic figures (P < 0.0001). In the no-imatinib treatment group, Ki-67 expression (P = 0.001) and KIT exon 11 mutation type (P < 0.001) were significantly correlated with recurrent metastasis. In the imatinib treatment group, Ki-67 expression (P = 0.01) and KIT exon 11 mutation type (P = 0.003) were significantly correlated with recurrent metastasis. Both Cox regression analysis and Kaplan-Meier survival analysis showed that patients with a Ki-67 score of ≥ 10 combined with deletion mutations in KIT exon 11 had a worse prognosis and shorter RFS than the patients with lower Ki-67 score and non-deletion mutations. The ROC curves showed that the new risk grading criteria containing Ki-67 and KIT exon 11 mutations better assessed patient prognosis (AUC = 0.715) compared to the NIH risk grading criteria (AUC = 0.715). Conclusions GIST patients with high Ki-67 expression levels combined with KIT exon 11 deletion mutation had a worse prognosis and could serve as a valuable prognostic marker complementary to the modified (2008) National Institute of Health (NIH) grading criteria for the prediction of the prognosis of high-risk GIST.