KIT 1530ins6 mutation defines a subset of predominantly malignant gastrointestinal stromal tumors of intestinal origin.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. GISTs express KIT and show gain-of-function KIT mutations. Most of these mutations affect the KIT juxtamembrane domain, but other KIT domains are mutated at a lower frequency. In this study, frequency of GCC TAT insertion mutation (1530ins6) in KIT exon 9 (extracellular domain) and its possible clinicopathologic significance was investigated. Screening of 520 GISTs identified 26 cases with 1530ins6 KIT mutation and confirmed the previously reported low frequency of this type of KIT mutation among GISTs of different locations. Of the 26 tumors with 1530ins6 KIT mutation studied, 21 originated from the small intestine, 1 from the colon, and 3 from the rectum. In 1 case, primary small intestinal versus colonic localization could not be clearly established because of intra-abdominal dissemination. No distinctive morphological features were identified for the cohort of tumors defined by 1530ins6 KIT mutations. Most of the tumors showed predominant spindle cell morphology, and a few cases had epithelioid or pleomorphic histological features. Following previously published criteria based on tumor size and mitotic rate, 22 of 26 (85%) tumors were classified as malignant or potentially malignant, and 4 (15%) were classified as probably benign. A malignant clinical course was documented in 18 of 19 tumors from the malignant category. The survival times of 11 patients who died of disseminated GISTs ranged from 1 month to 105 months (median survival time, 26 months). In contrast, 2 of 4 GISTs assigned as probably benign tumors with follow-up information had long disease-free survival. GISTs carrying 1530ins6 occur exclusively in the intestinal location, and a great majority of these tumors follow a malignant course.