Coexpression of biological key modulators in primary colorectal carcinomas and related metastatic sites: implications for treatment with cetuximab

Bull Cancer. 2010 Feb;97(2):E9-E15. doi: 10.1684/bdc.2010.1033.

Abstract

Background: Recent studies suggested substantial differences between primary tumors and metastases for EGFR expression in colorectal cancer (CRC). The aim of the study was to correlate the expression of a panel of molecular markers between primary CRC samples and metastases.

Methods: Expressions of EGFR, pEGFR, VEGF, pVEGF, PTEN, pAKT and p21 were analyzed in 28 primary tumors and 32 liver metastases by immunohistochemistry performed on formalin-fixed, paraffin-embedded sections from 46 CRC patients. The molecular profiles were evaluated by tissue micro-array. The correlation between tumor and metastasis biomarker expressions was tested.

Results: Among 60 CRC samples, 25% were EGFR positive, 38% were pEGFR positive, 38% were VEGF positive, 48% were pVEGF positive, 70% were pAKT positive and 51% were p21 positive. PTEN was deleted in 39% of cases and absence of p21 expression was found in 49% of cases. A significant correlation was observed between primary tumors and metastases for pAKT (p = 0.037) and pEGFR (p = 0.0002) status. In patients treated with cetuximab-based therapy (n = 18), p21 appeared as a significant predictive factor of response (p = 0.036).

Conclusion: Biomarkers status may change between primary and metastatic sites in CRC, with potential implications for the identification of patients who are likely to respond to anti-EGFR treatment.

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents / therapeutic use
  • Bevacizumab
  • Biomarkers, Tumor / metabolism*
  • Camptothecin / analogs & derivatives
  • Camptothecin / therapeutic use
  • Cetuximab
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / metabolism*
  • Cyclin-Dependent Kinase Inhibitor p21
  • ErbB Receptors / metabolism
  • Female
  • Humans
  • Irinotecan
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / secondary
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / secondary
  • Male
  • Middle Aged
  • Neoplasm Proteins / metabolism*
  • PTEN Phosphohydrolase / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Biomarkers, Tumor
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Neoplasm Proteins
  • Vascular Endothelial Growth Factor A
  • Bevacizumab
  • Irinotecan
  • ErbB Receptors
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • Cetuximab
  • Camptothecin