PURPOSE: Previous studies have reported clinical correlates for KIT mutations in GISTs, but in most of those studies the KIT mutations were found in less than 50% of the GISTs. The aim of this study was to evaluate the prognostic relevance for KIT mutations in a series of GISTs in which the mutations were evaluated intensively by genomic and cDNA sequencing. PATIENTS AND METHODS: A comprehensive clinical and pathologic analysis of 48 patients with GISTs who had snap-frozen tissue was performed. The median tumor size was 10 cm (range, 2 to 30 cm). Median follow-up for disease-free patients was 48 months. KIT genomic and cDNA was sequenced by using nucleic acid templates isolated from frozen tumors. RESULTS: The overall 5-year recurrence-free survival was 41% +/- 6%. Five-year recurrence-free survival for patients with tumors that had mitotic counts of three mitoses or fewer per 30 high-power fields (HPF), more than three to <or= 15 mitoses per 30 HPF, and more than 15 mitoses per 30 HPF were 89% +/- 7%, 49% +/- 12%, and 16% +/- 6%, respectively (P =.0001). The 32 patients with spindle-cell histology had a 49% +/- 7% 5-year recurrence-free survival; in contrast, the 16 patients with epithelioid or mixed histology had a 23% +/- 11% 5-year recurrence-free survival (P =.01). Five-year recurrence-free survival for patients with tumors less than 5 cm, 5 to 10 cm, and more than 10 cm were 82% +/- 12%, 45% +/- 9%, and 27% +/- 8%, respectively (P =.03). Prognostic associations were found with particular KIT mutation types, and patients with missense exon 11 mutations had a 5-year recurrence-free survival of 89% +/- 11% compared with 40% +/- 8% for GISTs with other mutation types (P =.03). The independent predictors for disease-free survival were the presence of deletion/insertion exon 11 mutations (hazard ratio [HR] = 4; P =.006), more than 15 mitoses per 30 HPF (HR = 18; P =.0001), mixed histology (HR = 21; P =.0001), and male sex (HR = 3; P =.05). CONCLUSION: In this series of KIT-expressing GISTs, tumor mitotic activity and histologic subtype were the most important prognostic features. The majority of GISTs contain KIT-activating mutations with the type/location of mutation serving as an independent predictor for disease-free survival. These results suggest that KIT mutation and activation are important in GIST pathogenesis and also may provide important prognostic information.
PURPOSE: Previous studies have reported clinical correlates for KIT mutations in GISTs, but in most of those studies the KIT mutations were found in less than 50% of the GISTs. The aim of this study was to evaluate the prognostic relevance for KIT mutations in a series of GISTs in which the mutations were evaluated intensively by genomic and cDNA sequencing. PATIENTS AND METHODS: A comprehensive clinical and pathologic analysis of 48 patients with GISTs who had snap-frozen tissue was performed. The median tumor size was 10 cm (range, 2 to 30 cm). Median follow-up for disease-free patients was 48 months. KIT genomic and cDNA was sequenced by using nucleic acid templates isolated from frozen tumors. RESULTS: The overall 5-year recurrence-free survival was 41% +/- 6%. Five-year recurrence-free survival for patients with tumors that had mitotic counts of three mitoses or fewer per 30 high-power fields (HPF), more than three to <or= 15 mitoses per 30 HPF, and more than 15 mitoses per 30 HPF were 89% +/- 7%, 49% +/- 12%, and 16% +/- 6%, respectively (P =.0001). The 32 patients with spindle-cell histology had a 49% +/- 7% 5-year recurrence-free survival; in contrast, the 16 patients with epithelioid or mixed histology had a 23% +/- 11% 5-year recurrence-free survival (P =.01). Five-year recurrence-free survival for patients with tumors less than 5 cm, 5 to 10 cm, and more than 10 cm were 82% +/- 12%, 45% +/- 9%, and 27% +/- 8%, respectively (P =.03). Prognostic associations were found with particular KIT mutation types, and patients with missense exon 11 mutations had a 5-year recurrence-free survival of 89% +/- 11% compared with 40% +/- 8% for GISTs with other mutation types (P =.03). The independent predictors for disease-free survival were the presence of deletion/insertion exon 11 mutations (hazard ratio [HR] = 4; P =.006), more than 15 mitoses per 30 HPF (HR = 18; P =.0001), mixed histology (HR = 21; P =.0001), and male sex (HR = 3; P =.05). CONCLUSION: In this series of KIT-expressing GISTs, tumor mitotic activity and histologic subtype were the most important prognostic features. The majority of GISTs contain KIT-activating mutations with the type/location of mutation serving as an independent predictor for disease-free survival. These results suggest that KIT mutation and activation are important in GIST pathogenesis and also may provide important prognostic information.
Authors: George D Demetri; Margaret von Mehren; Cristina R Antonescu; Ronald P DeMatteo; Kristen N Ganjoo; Robert G Maki; Peter W T Pisters; Chandrajit P Raut; Richard F Riedel; Scott Schuetze; Hema M Sundar; Jonathan C Trent; Jeffrey D Wayne Journal: J Natl Compr Canc Netw Date: 2010-04 Impact factor: 11.908
Authors: J F Emile; S Brahimi; J M Coindre; P P Bringuier; G Monges; P Samb; L Doucet; I Hostein; B Landi; M P Buisine; A Neuville; O Bouché; P Cervera; J L Pretet; J Tisserand; A Gauthier; A Le Cesne; J C Sabourin; J Y Scoazec; S Bonvalot; C L Corless; M C Heinrich; J Y Blay; P Aegerter Journal: Med Oncol Date: 2011-09-28 Impact factor: 3.064
Authors: Megan M Garrity; Simon J Gibbons; Thomas C Smyrk; Jean Marie Vanderwinden; Pedro Julian Gomez-Pinilla; Anoop Nehra; Matthew Borg; Gianrico Farrugia Journal: Histopathology Date: 2009-02 Impact factor: 5.087
Authors: Hiromichi Ito; Alexander Perez; David C Brooks; Robert T Osteen; Michael J Zinner; Francis D Moore; Stanley W Ashley; Edward E Whang Journal: J Gastrointest Surg Date: 2003-11 Impact factor: 3.452