title: Immunohistochemical profile and c-kit mutations in gastrointestinal stromal tumors.
abstract: Gastrointestinal stromal tumors (GISTs) are low-grade sarcomas arising from the interstitial cells of Cajal, harboring mutation of c-kit. We investigated the morphological, immunohistochemical, and molecular profile of 55 GISTs to establish the prevalence of mutations, their clinical significance, and diagnostic utility. c-kit mutations were investigated by evaluating the entire coding sequence of the gene with non-radioisotopic PCR-SSCP, and characterized with fluorescent cycle sequencing. Mutations were detected in 39 tumors (71%), the majority (67%) involving exon 11. Two tumors showed exon 9 mutations (one tumor located in the small intestine and one in the stomach), whereas two cases showed a polymorphism at the splicing site of exon/intron 1 present in healthy blood donors with a 3% frequency. CD117 was expressed in 53 tumors (96%); CD34 was positive in 42 cases (76%); 42 cases (76%) expressed both CD117 and CD34. c-kit mutations were similarly distributed in stromal tumors at low risk of aggressive behavior (78%), intermediate risk (66%), and high risk (71%). Fifteen tumors expressing CD117 showed wild-type kit gene, and on histological grounds, they were equally distributed among epithelioid and spindle cell morphology. One case neither expressed CD117 nor did it show c-kit mutation. Data suggest that both immunohistochemical and molecular evaluation may be useful in tumors likely to be classified as GISTs; molecular analysis appears valuable to support the diagnosis and to identify cases that can benefit from recent novel therapeutic tools.
authors.affiliation: II Department of Pathology, University of Milan School of Medicine, AOS Paolo, Via A. Di Rudini 8, 20142 Milano, Italy. solange.romagnoli@unimi.it
authors.forename: Solange
authors.initials: S
authors.lastname: Romagnoli
authors.forename: Daniela
authors.initials: D
authors.lastname: Graziani
authors.forename: Manuela
authors.initials: M
authors.lastname: Bramerio
authors.forename: Marcello
authors.initials: M
authors.lastname: Gambacorta
authors.forename: Piergiuseppe
authors.initials: P
authors.lastname: Colombo
authors.forename: Massimo
authors.initials: M
authors.lastname: Roncalli
authors.forename: Guido
authors.initials: G
authors.lastname: Coggi
authors.forename: Silvano
authors.initials: S
authors.lastname: Bosari
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000032:analysis; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics* / Q000378:metabolism*
chemical_list: D018952:Antigens, CD34; D014408:Biomarkers, Tumor; D019009:Proto-Oncogene Proteins c-kit