Prognostic and predictive values of the KIT11-mutated grading system in patients with gastrointestinal stromal tumors: a retrospective study

• Published in: Human pathology 2021-04, Vol.110, p.31-42
• Main Authors: Song, Ling-Jun, Ge, Hui-Juan, Shi, Xiao-Qin, Shen, Wei-Wei
• Format: Article
• Language: English
• Subjects: Deoxyribonucleic acid; DNA; Gastrointestinal cancer; Gastrointestinal stromal tumor; Imatinib resistance; KIT11 mutation; Large intestine; Medical prognosis; Mutation; Prognosis; Small intestine; Statistical analysis; Stomach; Targeted cancer therapy; Tumors
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2021.01.001

The KIT11 mutation is the most frequent mutation pattern in gastrointestinal stromal tumors (GISTs). However, few studies have investigated the correlation between the KIT11-mutated grading system and imatinib mesylate (IM) sensitivity (the first choice for adjuvant treatment of GISTs). Here, we elucidated the clinical value of the KIT11-mutated grading system for prognostic prediction in patients with GISTs treated with IM. A total of 106 patients with GIST were treated with IM (8: intermediate-risk, 98: high-risk; 10: KIT9-mutated, 86: KIT11-mutated, 5: wild-type, and 5: other mutations). KIT11-mutated patients were divided into 3 grades based on the KIT11-mutated site and type. Clinical backgrounds and prognostic outcomes were retrospectively compared between the 3 groups. Of 86 KIT11-mutated patients treated with IM, 32 (37.21%) had grade 1 tumors, 37 (43.02%) had grade 2 tumors, and 17 (19.77%) had grade 3 tumors. The 5-year disease-free survival (DFS) was significantly worse in patients with grade 3 KIT11-mutated GISTs (41.96%, p = 0.001) than in those with grade 1 (93%) and grade 2 (70.64%) cases. The multivariable analysis suggested that the KIT11-mutated grading system was an independent risk factor for DFS in patients treated with IM (hazard risk, 2.512; 95% confidence interval, 1.370–4.607; p = 0.003). In conclusion, the KIT11-mutated grading system provides good prognostic stratification for DFS in patients treated with IM. Grade 1 tumors predict a favorable response to IM. •The KIT11-mutated grading system was established based on the mutation site and type of KIT11 mutation.•The KIT11-mutated grading system provides good prognostic stratification for disease-free survival in patients treated with imatinib mesylate.•KIT9-mutated and grade 2 and grade 3 KIT11-mutated tumors showed more aggressive behavior with poor prognosis.