PURPOSE: Previous studies have reported clinical correlates for @entity2467 mutations in GISTs, but in most of those studies the @entity2467 mutations were found in less than 50% of the GISTs. The aim of this study was to evaluate the prognostic relevance for @entity2467 mutations in a series of GISTs in which the mutations were evaluated intensively by genomic and cDNA sequencing. @entity1 AND METHODS: A comprehensive clinical and pathologic analysis of 48 @entity1 with GISTs who had snap-frozen tissue was performed. The median @entity5 size was 10 cm (range, 2 to 30 cm). Median follow-up for disease-free @entity1 was 48 months. @entity2467 genomic and cDNA was sequenced by using nucleic acid templates isolated from frozen @entity5 . RESULTS: The overall 5-year recurrence-free survival was 41% +/- 6%. Five-year recurrence-free survival for @entity1 with @entity5 that had mitotic counts of three mitoses or fewer per 30 @entity2194 ( @entity2194 ), more than three to <or= 15 mitoses per 30 @entity2194 , and more than 15 mitoses per 30 @entity2194 were 89% +/- 7%, 49% +/- 12%, and 16% +/- 6%, respectively (P =.0001). The 32 @entity1 with spindle-cell histology had a 49% +/- 7% 5-year recurrence-free survival; in contrast, the 16 @entity1 with epithelioid or mixed histology had a 23% +/- 11% 5-year recurrence-free survival (P =.01). Five-year recurrence-free survival for @entity1 with @entity5 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 @entity2467 mutation types, and @entity1 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 @entity2194 (HR = 18; P =.0001), mixed histology (HR = 21; P =.0001), and male sex (HR = 3; P =.05). CONCLUSION: In this series of @entity2467 -expressing GISTs, @entity5 mitotic activity and histologic subtype were the most important prognostic features. The majority of GISTs contain @entity2467 -activating mutations with the type/location of mutation serving as an independent predictor for disease-free survival. These results suggest that @entity2467 mutation and activation are important in GIST pathogenesis and also may provide important prognostic information.

Prognostic value of XXXX mutation type, mitotic activity, and histologic subtype in gastrointestinal stromal tumors.

@entity1 :: ('9606', 'Species') :: ['patients', 'PATIENTS'] @entity2194 :: ('MESH:D005128', 'Disease') :: ['HPF', 'high-power fields'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'tumors'] @entity2467 :: ('3815', 'Gene') :: ['KIT']
@entity2467 :: (3815,Gene) :: ['KIT']
