title: Telomerase activity as prognostic factor in gastrointestinal stromal tumors of the stomach.
abstract: OBJECTIVE
  Although size and mitotic counts have been reliable predictors of clinical outcome, identification of gastrointestinal stromal tumor (GIST) of the stomach with a metastatic potential through hematoxylin and eosin staining is not always accurate. Telomerase activity, often detected in malignant tumors, may have a role as a marker for high-grade malignancy.
  
  
  METHODS
  Immunostaining with antibodies against KIT protein, CD34, and other molecules that are relevant for evaluation of cell differentiation and proliferation was performed for 36 primary gastric submucosal tumors to confirm the diagnosis of GIST. DNA was extracted from the surgically resected specimens of 24 of 36 patients, and c-kit mutation was analyzed by direct sequencing after PCR amplification of the exon 11. Telomerase activity was quantitatively evaluated for all 36 patients using fluorescence-based telomeric amplification assay protocol (TRAP) analysis.
  
  
  RESULTS
  c-kit mutation was observed in 58% of the patients evaluated. Telomerase activity was detected in 14 specimens (39%), but not in the specimens without c-kit mutation. All 5 patients who suffered from metastatic or recurrent disease exhibited c-kit mutation and a high level of telomerase activity.
  
  
  CONCLUSIONS
  Measurement of telomerase activity, along with c-kit mutation analysis, is useful for identifying GIST with a potential for malignant behavior.
authors.affiliation: Department of Surgery II, Nagoya University Graduate School of Medicine, Nagoya University Hospital, Nagoya, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kawai
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kodera
authors.forename: Michitaka
authors.initials: M
authors.lastname: Fujiwara
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kasai
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Nagasaka
authors.forename: Masahiko
authors.initials: M
authors.lastname: Koike
authors.forename: Kenji
authors.initials: K
authors.lastname: Hibi
authors.forename: Katsuki
authors.initials: K
authors.lastname: Ito
authors.forename: Seiji
authors.initials: S
authors.lastname: Akiyama
authors.forename: Akimasa
authors.initials: A
authors.lastname: Nakao
mesh_terms: D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000032:analysis / Q000235:genetics; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000235:genetics / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D008940:Mitotic Index; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis / Q000235:genetics; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology*; D019098:Telomerase / Q000032:analysis* / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics
chemical_list: D018952:Antigens, CD34; D014408:Biomarkers, Tumor; D016159:Tumor Suppressor Protein p53; D019009:Proto-Oncogene Proteins c-kit; D019098:Telomerase