Impact of E2F-1 expression on clinical outcome of gastric adenocarcinoma patients with adjuvant chemoradiation therapy.
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.
Lee
Jeeyun
J
Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Park
Cheol Keun
CK
Park
Joon Oh
JO
Lim
Taekyu
T
Park
Young Suk
YS
Lim
Ho Yeong
HY
Lee
Inkyoung
I
Sohn
Tae Sung
TS
Noh
Jae Hyung
JH
Heo
Jin Seok
JS
Kim
Sung
S
Lim
Do Hoon
DH
Kim
Kyoung-Mee
KM
Kang
Won Ki
WK
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
D050687:E2F1 Transcription Factor; D013940:Thymidylate Synthase; D002955:Leucovorin; D005472:Fluorouracil