Ki-67 labeling index may be a promising indicator to identify “very high-risk” gastrointestinal stromal tumor: a multicenter retrospective study of 1022 patients

Abstract

We sought to determine whether Ki-67 labeling index (LI) was an independent prognostic factor for gastrointestinal stromal tumor (GIST). A multicenter cohort of 1022 patients undergoing surgical resection of primary GIST between August 2004 and October 2015 was retrospectively analyzed. Immunohistochemical analysis was performed to evaluate expression of Ki-67 in their paraffin-embedded tissue samples. The optimal cutoff value of Ki-67 LI was determined as 6% by receiver operating characteristics curve analysis. Multivariate analysis showed that Ki-67 LI was a significant predictor of overall survival (OS) (hazard ratio: 1.793; 95% confidence interval, 1.240-2.593; P=.002). When stratified by modified National Institutes of Health classification, it was still independently associated with OS in high-risk and non-high-risk patients (P=.001 and P=.055, respectively). Of note, the prognostic significance of Ki-67 LI was also maintained when stratified by tumor size, mitotic index, tumor site, and histological subtype (all Ps<.05). In addition, high-risk patients with Ki-67 LI >6% exhibited a significantly poorer OS rate than those with Ki-67 LI ≤6% (53.6% versus 88.7%, respectively; P=.001). The area under the receiver operating characteristics curve for Ki-67 LI was higher than that of modified National Institutes of Health classification component in high-risk patients (P=.029). Therefore, Ki-67 LI is a promising predictor of outcome in GIST, especially in high-risk patients, and it may have important clinical utility in identifying "very high-risk" patients for rational targeted therapy.