Epidermal growth factor receptor (EGFR) status in primary colorectal tumors does not correlate with EGFR expression in related metastatic sites: implications for treatment with EGFR-targeted monoclonal antibodies

J Clin Oncol. 2004 Dec 1;22(23):4772-8. doi: 10.1200/JCO.2004.00.117.

Abstract

Purpose: We hypothesized that the detection of epidermal growth factor receptor (EGFR) expression performed in primary tumors for treatment with EGFR-targeted monoclonal antibodies could not always correlate with EGFR status in metastatic sites, thus making cancer cells in these sites resistant to therapy. The aim of our study was to correlate EGFR expression on primary tumors and related metastases in order to find out whether assessing EGFR status on primary cancer is to be considered an effective tool for planning treatment with EGFR-targeted antibodies.

Patients and methods: We retrospectively evaluated EGFR immunohistochemistry from primary tumors and related metastatic sites in 99 colorectal cancer patients. The site of primary tumor was colon in 77 patients (78%) and rectum in 22 patients (22%). Metastatic sites analyzed were liver in 84 patients (81%), lung in 13 patients (13%), bone in one patient (1%), and brain in five patients (5%). EGFR status was defined as positive if the percentage of malignant cells stained was > or = 1%.

Results: EGFR status was positive in 53 primary tumors (53%). In 19 primary tumors expressing EGFR (36%), the corresponding metastatic site was found negative, whereas it was found positive in seven metastases (15%) from EGFR-negative primary cancers. The difference between these two groups of patients (ie, EGFR-positive to EGFR-negative v EGFR-negative to EGFR-positive) was statistically significant (P = .036).

Conclusion: Our results suggest that the detection of the EGFR in primary colorectal cancer could be inadequate for planning therapy with EGFR-targeted monoclonal antibodies in a considerable proportion of both EGFR-positive and -negative primary tumors (36% and 15%, respectively).

Publication types

  • Comparative Study

MeSH terms

  • Adenocarcinoma / mortality
  • Adenocarcinoma / pathology
  • Adenocarcinoma / secondary*
  • Adenocarcinoma / therapy*
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / therapeutic use*
  • Biomarkers, Tumor / metabolism
  • Biopsy, Needle
  • Cohort Studies
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology*
  • Colorectal Neoplasms / therapy*
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Immunotherapy / methods
  • Male
  • Middle Aged
  • Neoplasm Invasiveness / pathology
  • Neoplasm Staging
  • Probability
  • Prognosis
  • Retrospective Studies
  • Risk Assessment
  • Sensitivity and Specificity
  • Survival Analysis
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Biomarkers, Tumor
  • ErbB Receptors