title: Uterine sarcomas express KIT protein but lack mutation(s) in exon 11 or 17 of c-KIT.
abstract: OBJECTIVE
  Several tumors express the protein product of the protooncogene c-KIT. Some of these respond to imatinib mesylate, a tyrosine kinase inhibitor. The tumors that respond frequently have mutation(s) in exon 11 of c-KIT that encodes for the regulatory juxtamembrane helix. Some tumors that express KIT protein have mutation(s) in exon 17 of c-KIT; however, these do not respond to imatinib mesylate. This investigation was performed to determine the expression of KIT protein and mutational status of exons 11 and 17 of c-KIT in uterine sarcomas.
  
  
  METHODS
  Twenty-five uterine sarcomas treated from 1990 to 2002 were evaluated. These included 14 malignant mullerian mixed tumors (MMMT), 7 leiomyosarcomas (LMS), 2 endometrial stromal sarcomas (ESS), and 2 high-grade heterologous sarcomas (HGHS). Formalin-fixed, paraffin-embedded tissue sections were immunostained with anti-KIT antibody (Santa Cruz Biotechnology, Santa Cruz, CA) with a semiquantitative assessment. Normal myometrium when present in the section was used as an internal negative control. Areas of tumor were microdissected followed by DNA extraction, polymerase chain reaction (PCR) amplification of exons 11 and 17, single-strand conformational polymorphism (SSCP), and DNA sequencing to detect the presence of mutation(s).
  
  
  RESULTS
  All 25 tumors expressed KIT protein at varying levels as assessed by immunohistochemistry. The staining was diffuse and of moderate to strong intensity in 22 tumors. In three tumors (one of each type except MMMT) the staining intensity was weak. In MMMT the epithelial and sarcomatous foci stained similarly. No mutation(s) in exons 11 or 17 of c-KIT were identified in 24/25 tumors. One LMS had deletion of both exons 11 and 17.
  
  
  CONCLUSIONS
  Although uterine sarcomas express KIT protein, they lack KIT-activating mutation(s) in exon 11 or 17 of c-KIT. Therefore, these tumors are unlikely to respond to imatinib mesylate.
authors.affiliation: Division of Gynecologic Oncology, University of Kentucky College of Medicine, Lexington, KY 40536, USA.
authors.forename: R Scott
authors.initials: RS
authors.lastname: Rushing
authors.forename: Shahin
authors.initials: S
authors.lastname: Shajahan
authors.forename: Damodaran
authors.initials: D
authors.lastname: Chendil
authors.forename: James L
authors.initials: JL
authors.lastname: Wilder
authors.forename: Joseph
authors.initials: J
authors.lastname: Pulliam
authors.forename: Eun Y
authors.initials: EY
authors.lastname: Lee
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Ueland
authors.forename: John R
authors.initials: JR
authors.lastname: van Nagell
authors.forename: Mansoor M
authors.initials: MM
authors.lastname: Ahmed
authors.forename: Subodh M
authors.initials: SM
authors.lastname: Lele
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004273:DNA, Neoplasm / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007890:Leiomyosarcoma / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D018200:Mixed Tumor, Mullerian / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis* / Q000235:genetics*; D012509:Sarcoma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D018203:Sarcoma, Endometrial Stromal / Q000235:genetics / Q000378:metabolism; D014594:Uterine Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology
chemical_list: D004273:DNA, Neoplasm; D019009:Proto-Oncogene Proteins c-kit