[Impact of HER2, EGFR, IGF-1R, and VEGFR expressions on the outcome of chemotherapy for advanced gastric cancer].
We aimed to elucidate the clinical significance of the expressions of HER2, epidermal growth factor receptor (EGFR), insulin-like growth factor receptor (IGF-1R), and vascular endothelial growth factor receptor 1, 2, 3 (VEGF-R1, VEGF-R2, and VEGF-R3) in gastric cancer. The study group comprised 57 patients who had undergone gastrectomy at the National Cancer Center Hospital and subsequently received first-line chemotherapy (S-1 monotherapy [n=29] or irinotecan+cisplatin [n=28]) for recurrent or residual tumors. We performed immunohistochemical analysis of formalin-fixed paraffinembedded specimens of surgically removed primary tumors to determine the expressions of HER2, EGFR, IGF-1R, and VEGFR1 in tumor cells and the expressions of VEGF-R1, VEGF-R2, and VEGF-R3 in tumor stromal vessels. The expressions of HER2 (p=0.017) and IGF-1R (p=0.025) were significantly more common in intestinal type tumors than in diffuse type. The protein expressions did not correlate with tumor response in either chemotherapy-regimen group. Among the patients who underwent S-1 monotherapy, those with cytoplasmic VEGF-R1-positive tumors had significantly shorter progression-free survival (logrank, p=0.017). In the survival analysis of all the patients, coexpression of membranous IGF-1R and VEGF-R3 in stromal vessels was the most significant predictor of poor survival (hazard ratio, 1.82; 95% CI, 1.31-2.63; p<0.001). The results of our study will facilitate more efficient use of molecular targeted agents in patients with gastric cancer.
Matsubara
Junichi
J
Chemotherapy Division, National Cancer Center Research Institute.
Hirashima
Yoshinori
Y
Yamada
Yasuhide
Y
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D015996:Survival Rate; D016896:Treatment Outcome
D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; D017526:Receptor, IGF Type 1; D040262:Receptors, Vascular Endothelial Growth Factor; C512478:EGFR protein, human; C508053:ERBB2 protein, human