title: Reduced survival of rectal cancer patients with increased tumor epidermal growth factor receptor levels.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgery, Klinikum Grosshadern, University of Munich, Munich, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Kopp
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Rothbauer
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Mueller
authors.forename: Friedrich Wilhelm
authors.initials: FW
authors.lastname: Schildberg
authors.forename: Karl-Walter
authors.initials: KW
authors.lastname: Jauch
authors.forename: Andreas
authors.initials: A
authors.lastname: Pfeiffer
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D002277:Carcinoma / Q000737:chemistry / Q000401:mortality; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000401:mortality / Q000473:pathology; D066246:ErbB Receptors / Q000032:analysis*; D006801:Humans; D007413:Intestinal Mucosa / Q000737:chemistry; D008207:Lymphatic Metastasis; D009361:Neoplasm Invasiveness; D011379:Prognosis; D011869:Radioligand Assay; D012004:Rectal Neoplasms / Q000737:chemistry / Q000401:mortality* / Q000473:pathology; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D066246:ErbB Receptors