Differential expression of biomarkers in primary non-small cell lung cancer and metastatic sites

J Thorac Oncol. 2009 Oct;4(10):1212-20. doi: 10.1097/JTO.0b013e3181b44321.

Abstract

Introduction: The use of biomarkers to evaluate the presence of a target or to select a specific therapy is increasingly advocated. The correlation of biomarker expression between the primary tumor and its corresponding metastasis has not yet been well documented and analyzed in patients with non-small cell lung cancer (NSCLC).

Methods: The expression of epidermal growth factor receptor (EGFR), excision repair cross-complementing (ERCC1), vascular-endothelial growth factor receptor, and Ki-67 was immunohistochemically analyzed in tumor samples of primary NSCLC and one corresponding metastasis in a population of 49 patients.

Results: Sixteen cases (33%) displayed clear discordance in the EGFR status between the primary tumor and the metastasis, with a significant trend toward downregulation of EGFR in the metastasis (p = 0.01). The ERCC1 status was discordant in 20 cases (41%), with a trend toward overexpression in brain and adrenal metastases (p = 0.01 and p = 0.08, respectively). The vascular-endothelial growth factor receptor and Ki-67 statuses were discordant in 13 (27%) and 15 (31%) cases, respectively. No difference in expression was observed between synchronous and metachronous metastasis.

Conclusion: Biomarker expression is discordant between the primary tumor and its corresponding metastasis in about one third of patients with NSCLC. These findings should be considered in the setting of clinical trials and further explored using frozen material and high-throughput techniques.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Adenocarcinoma, Bronchiolo-Alveolar / metabolism
  • Adenocarcinoma, Bronchiolo-Alveolar / pathology
  • Adrenal Gland Neoplasms / metabolism*
  • Adrenal Gland Neoplasms / secondary
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Bone Neoplasms / metabolism*
  • Bone Neoplasms / secondary
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / secondary
  • Carcinoma, Large Cell / metabolism
  • Carcinoma, Large Cell / pathology
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • DNA-Binding Proteins / metabolism
  • Endonucleases / metabolism
  • ErbB Receptors / metabolism
  • Female
  • Humans
  • Immunoenzyme Techniques
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Receptors, Vascular Endothelial Growth Factor / metabolism
  • Survival Rate
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • EGFR protein, human
  • ErbB Receptors
  • Receptors, Vascular Endothelial Growth Factor
  • ERCC1 protein, human
  • Endonucleases