title: Impact of E2F-1 expression on clinical outcome of gastric adenocarcinoma patients with adjuvant chemoradiation therapy.
abstract: OBJECTIVE
  There are no reliable prognostic markers that identify gastric cancer patients who may benefit from adjuvant chemoradiation therapy. E2F-1 was shown to be associated with radiosensitivity and chemosensitivity in certain tumor types. Therefore, we analyzed expression and prognostic significance of E2F-1 along with thymidylate synthase (TS) in R(0)-resected gastric adenocarcinoma patients, who underwent adjuvant chemoradiation therapy with 5-fluorouracil (5-FU) and leucovorin.
  
  
  METHODS
  The chemosensitivity to 5-FU and radiosensitivity were tested in three E2F-1-overexpressed gastric cancer cell lines in vitro. The expressions of TS and E2F-1 were analyzed in 467 R(0)-resected primary gastric cancer patients, who received adjuvant chemoradiation therapy with 5-FU and leucovorin using tissue microarray.
  
  
  RESULTS
  The E2F-1 immunopositivity rate was 22.2% (103 of 465 samples) with a cutoff value of 5% immunoreactivity, whereas the TS-positive expression occurred in 19.0% of the 463 tumors tested. Using stepwise Cox proportional hazards regression modeling, multivariate analyses showed that the E2F-1 immunopositivity predicted more favorable survival as compared with the E2F-1 immunonegativity with borderline statistical significance [P = 0.050, hazard ratio (HR) = 0.702, 95% confidence interval, 0.487, 1.013]. However, the E2F-1 immunopositivity did not retain its statistical significance at multivariate analysis for predicting disease-free survival (data not shown, P = 0.270), but stage was the only influential factor for disease-free survival in stages IB to IV (M(0)) patients (P < 0.001). TS immunopositivity did not influence survival (P = 0.459) or disease-free survival (P = 0.447).
  
  
  CONCLUSIONS
  E2F-1 is a potentially novel independent prognostic factor that may identify gastric cancer patients who will likely benefit from adjuvant chemoradiation therapy following curative resection.
authors.affiliation: Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Jeeyun
authors.initials: J
authors.lastname: Lee
authors.forename: Cheol Keun
authors.initials: CK
authors.lastname: Park
authors.forename: Joon Oh
authors.initials: JO
authors.lastname: Park
authors.forename: Taekyu
authors.initials: T
authors.lastname: Lim
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Park
authors.forename: Ho Yeong
authors.initials: HY
authors.lastname: Lim
authors.forename: Inkyoung
authors.initials: I
authors.lastname: Lee
authors.forename: Tae Sung
authors.initials: TS
authors.lastname: Sohn
authors.forename: Jae Hyung
authors.initials: JH
authors.lastname: Noh
authors.forename: Jin Seok
authors.initials: JS
authors.lastname: Heo
authors.forename: Sung
authors.initials: S
authors.lastname: Kim
authors.forename: Do Hoon
authors.initials: DH
authors.lastname: Lim
authors.forename: Kyoung-Mee
authors.initials: KM
authors.lastname: Kim
authors.forename: Won Ki
authors.initials: WK
authors.lastname: Kang
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000628:therapy*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015153:Blotting, Western; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D013505:Digestive System Surgical Procedures; D018572:Disease-Free Survival; D050687:E2F1 Transcription Factor / Q000096:biosynthesis*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D018714:Radiotherapy, Adjuvant; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000628:therapy*; D016019:Survival Analysis; D013940:Thymidylate Synthase / Q000096:biosynthesis; D046888:Tissue Array Analysis; D016896:Treatment Outcome
chemical_list: D050687:E2F1 Transcription Factor; D013940:Thymidylate Synthase; D002955:Leucovorin; D005472:Fluorouracil