Reduced survival of rectal cancer patients with increased tumor epidermal growth factor receptor levels

Abstract

Purpose: The epidermal growth factor receptor and its various ligands (epidermal growth factor, transforming growth factor-alpha, amphiregulin, heparin-binding epidermal growth factor, heregulin, and betacellulin) have been implicated in growth and regeneration of intestinal mucosa and might be related to the development and progression of gastrointestinal tumors. Although some studies have investigated levels of epidermal growth factor receptor by radioligand binding studies, none of them have further analyzed these levels in patients with rectal cancer and investigated their prognostic value.

Methods: We quantitatively determined tumor epidermal growth factor receptor levels in 38 patients with colorectal cancer compared with adjacent normal mucosa by iodine-125-labeled epidermal growth factor binding studies and Scatchard analysis. Patients were followed up for 49.5 +/- 32.2 (range, 2-120) months.

Results: Epidermal growth factor receptor capacity was increased in invasive colorectal carcinomas according to T classification (P < 0.001), tumors with lymph node infiltration (P = 0.038), and advanced International Union Against Cancer stage (P < 0.001). Survival of colorectal cancer was reduced in patients with advanced International Union Against Cancer stage (P < 0.001), tumors with positive lymph nodes (P < 0.001), and tumors with elevated epidermal growth factor receptor levels (P = 0.024). In rectal cancer patients, poor prognosis was associated with advanced International Union Against Cancer stage (P = 0.029), tumors with lymph node infiltration (P = 0.040), and increased epidermal growth factor receptor levels (P = 0.002). Multivariate Cox regression analysis indicated that elevated levels of epidermal growth factor receptor were an independent predictor of reduced survival in patients with rectal cancer (P = 0.005).

Conclusion: The epidermal growth factor receptor/ligand system appears to be involved in tumor development and tumor progression of colorectal carcinomas, with prognostic implication especially in patients with invasive rectal carcinomas. These patients might take advantage of therapies that specifically block epidermal growth factor receptor-mediated signal transduction.