title: The prognostic value of pfetin: a validation study in gastrointestinal stromal tumors using a commercially available antibody.
abstract: OBJECTIVE
  Adjuvant treatment with imatinib mesylate is an effective treatment for gastrointestinal stromal tumor. However, 50% of patients with gastrointestinal stromal tumor can be cured by surgery alone; hence, risk stratification for therapy with imatinib mesylate is the next challenge. Previously, using a proteomic approach, we discovered a potential prognostic biomarker for gastrointestinal stromal tumor, pfetin, and immunohistochemically validated its clinical utility using our original monoclonal antibody. In the present study, we examine the usefulness of a commercially available polyclonal antibody against pfetin.
  
  
  METHODS
  Western blotting and immunohistochemistry were performed using surgical specimens of primary tissues from gastrointestinal stromal tumor patients using a polyclonal antibody against pfetin and our original monoclonal antibody. Formalin-fixed and paraffin-embedded primary tissue sections from 112 gastrointestinal stromal tumor patients were subjected to immunohistochemistry. The immunohistochemistry results were integrated with the clinico-pathological observations.
  
  
  RESULTS
  Western blotting revealed that both antibodies recognized multiple post-translationally modified pfetin isoforms. The immunohistochemical study with the commercial antibody demonstrated that the disease-free survival rate was 88 and 56% for pfetin-positive and pfetin-negative patients, respectively. Univariate and multivariate analyses showed that pfetin expression as measured by the commercial antibody was a significant and independent prognostic factor among the clinico-pathological parameters examined. Of the 112 gastrointestinal stromal tumor cases examined, 13 yielded discordant results between the commercial antibody and our original antibody, and there were no significantly different clinical or pathological factors to account for this discrepancy.
  
  
  CONCLUSIONS
  Our observations suggest that the pfetin expression level assessed by the commercial antibody could be a prognostic biomarker in gastrointestinal stromal tumors.
authors.affiliation: Division of Pharmacoproteomics, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kubota
authors.forename: Kenta
authors.initials: K
authors.lastname: Mukaihara
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshida
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Suehara
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Saito
authors.forename: Taketo
authors.initials: T
authors.lastname: Okubo
authors.forename: Masahiro
authors.initials: M
authors.lastname: Gotoh
authors.forename: Hajime
authors.initials: H
authors.lastname: Orita
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Tsuda
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kaneko
authors.forename: Akira
authors.initials: A
authors.lastname: Kawai
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kondo
authors.forename: Koichi
authors.initials: K
authors.lastname: Sato
authors.forename: Takashi
authors.initials: T
authors.lastname: Yao
mesh_terms: D000368:Aged; D000906:Antibodies; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000378:metabolism* / Q000401:mortality* / Q000601:surgery; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D011506:Proteins / Q000032:analysis* / Q000276:immunology*; D016019:Survival Analysis
chemical_list: D000906:Antibodies; D014408:Biomarkers, Tumor; C493175:KCTD12 protein, human; D011506:Proteins
keywords: antibody; biomarker; gastrointestinal stromal tumor; pfetin