Relationship of insulin-like growth factor-1 receptor and epidermal growth factor receptor expression to clinical outcomes in patients with colorectal cancer

Abstract

4117 Background: Insulin-like growth factor-1 receptor (IGF-1R), epidermal growth factor receptor (EGFR), and HER2 have been reported to regulate tumor growth by interfering with apoptosis, cell proliferation, angiogenesis, and metastasis. However, the clinical significance of these molecules in colorectal cancer (CRC) remains undetermined. To gain further insight, we evaluated the prognostic implications of these biomarkers in patients with CRC treated with fluoropyrimidines or irinotecan. Methods: The study group comprised 91 patients who underwent surgery at National Cancer Center Hospital and subsequently received fluoropyrimidines as 1st-line chemotherapy for recurrent or residual tumors. The expressions of IGF-1R, EGFR, and HER2 in surgically removed specimens of primary lesions were analyzed immunohistochemically to determine the prognostic significance of these biomarkers. Results: IGF-1R expression (defined as >10% membranous staining) was found in 81 tumors (89%), EGFR in 77 (85%), and HER2 in 3 (3%). IGF-1R expression significantly correlated with EGFR expression (P=0.038). Overexpression (defined as >50% membranous staining) of IGF-1R was found in 48 tumors (53%), EGFR in 57 (63%), and HER2 in 2 (2%). Overexpression of IGF-1R significantly correlated with shorter survival from the start of 1st-line chemotherapy (P=0.032). Overexpression of EGFR was a significant predictive factor for a clinical response to fluoropyrimidines (P=0.037) and tended to correlate with TTP in patients given irinotecan as 2nd-line therapy (P=0.087). A multivariate analysis of potential prognostic factors showed that IGF-1R expression and worse performance status were independent predictors of poor outcomes ( Table ). Conclusions: IGF-1R and EGFR were highly positive in patients with CRC. Overexpression of IGF-1R predicts a poor outcome, and overexpression of EGFR predicts a good clinical response to fluoropyrimidines. [Table: see text] No significant financial relationships to disclose.