Clinical significance of insulin-like growth factor type 1 receptor and epidermal growth factor receptor in patients with advanced gastric cancer.
OBJECTIVE
To better understand the clinical implications of insulin-like growth factor type 1 receptor (IGF-1R), epidermal growth factor receptor (EGFR) and HER2 expressions in gastric cancer (GC).


METHODS
The study group comprised 86 patients who received first-line chemotherapy for advanced GC at the National Cancer Center Hospital. Using laser-captured microdissection and a real-time RT-PCR assay, we quantitatively evaluated mRNA levels of IGF-1R, EGFR and HER2 in paraffin-embedded cancer specimens of surgically removed primary tumors.


RESULTS
In univariate analysis of the study group as a whole, patients with low expression of both IGF-1R and EGFR (n = 13) had a significantly longer overall survival than the other patients (n = 51; median, 24.6 vs. 12.8 months; log-rank p = 0.013). Multivariate survival analysis demonstrated that high EGFR expression [hazard ratio, HR: 2.94 (95% confidence interval, CI: 1.40-6.17), p = 0.004] and poor performance status [HR: 1.96 (95% CI: 1.12-3.42), p = 0.018] were significant predictors of poor survival. In patients given first-line S-1 monotherapy (n = 29), low IGF-1R (p = 0.002) and low EGFR (p = 0.035) gene expression correlated with a better response, without a significant prolongation of survival.


CONCLUSIONS
Our data warrant further investigations on the strategy of co-targeting IGF-1R and EGFR in GC.
Matsubara
Junichi
J
Division of Gastrointestinal Oncology, National Cancer Center Hospital, Tokyo, Japan.
Yamada
Yasuhide
Y
Nakajima
Takako E
TE
Kato
Ken
K
Hamaguchi
Tetsuya
T
Shirao
Kuniaki
K
Shimada
Yasuhiro
Y
Shimoda
Tadakazu
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D016019:Survival Analysis
D000970:Antineoplastic Agents; D066246:ErbB Receptors; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D017526:Receptor, IGF Type 1