title: Prognostic impact of major receptor tyrosine kinase expression in gastric cancer.
abstract: BACKGROUND
  Various kinds of molecular targeted drugs to inhibit receptor tyrosine kinases (RTKs) have been recently developed. The relationship between the expression status of major RTKs and prognosis in gastric cancer remains unclear. We conducted a multicenter study to evaluate the prognostic impact of the expression of epidermal growth factor receptor (EGFR), c-Met, platelet-derived growth factor receptor (PDGFR), and c-Kit in gastric cancer.
  
  
  METHODS
  This study included 153 gastric cancer patients who underwent gastrectomy at 9 institutions between 2000 and 2006. Expression status of EGFR, c-Met, PDGFR, and c-Kit were evaluated with immunohistochemistry (IHC) centrally. Overall survival based on RTK expression status was statistically compared. Cox multivariate analysis was conducted to adjust for potentially confounding factors.
  
  
  RESULTS
  The positive rates for EGFR, c-Met, PDGFR, and c-Kit were 14.4, 24.8, 41.2, and 11.1 %, respectively. Significant interactions with expression status were observed for pathological N stage with EGFR; HER2-status with c-Met; tumor location, histology, and pathological N stage with PDGFR; and no examined variables with c-Kit. Concomitant HER2 positivity was observed for 0.7 % of tumors positive for EGFR, 3.9 % for c-Met, 4.6 % for PDGFR, and 1.3 % for c-Kit. There were some differences in overall survival between patients with or without RTK expression, but only c-Kit expression showed a significant survival difference in Cox multivariate analysis (P = 0.046).
  
  
  CONCLUSIONS
  Our multicenter study indicated that IHC expression of 4 RTKs had some prognostic impact and that c-Kit-positive status may be a significant indicator of good prognosis in gastric cancer patients.
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan, ykurokawa@gesurg.med.osaka-u.ac.jp.
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Kurokawa
authors.forename: Nariaki
authors.initials: N
authors.lastname: Matsuura
authors.forename: Ryohei
authors.initials: R
authors.lastname: Kawabata
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nishikawa
authors.forename: Chikara
authors.initials: C
authors.lastname: Ebisui
authors.forename: Yuhki
authors.initials: Y
authors.lastname: Yokoyama
authors.forename: Mohammed Nouri
authors.initials: MN
authors.lastname: Shaker
authors.forename: Takuya
authors.initials: T
authors.lastname: Hamakawa
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Takahashi
authors.forename: Shuji
authors.initials: S
authors.lastname: Takiguchi
authors.forename: Masaki
authors.initials: M
authors.lastname: Mori
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Doki
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry* / Q000473:pathology* / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D005743:Gastrectomy; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D017479:Receptors, Platelet-Derived Growth Factor / Q000032:analysis; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000737:chemistry* / Q000473:pathology* / Q000601:surgery; D015996:Survival Rate
chemical_list: D066246:ErbB Receptors; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor; C080835:RON protein