Clinical application of biological markers for treatments of resectable non-small-cell lung cancers

Br J Cancer. 2005 Apr 11;92(7):1231-9. doi: 10.1038/sj.bjc.6602481.

Abstract

We performed a clinical study to identify biological markers useful for the treatment of resectable non-small-cell lung cancers (NSCLCs). In all, 173 patients were studied. By immunohistochemistry, we evaluated the Ki-67 proliferation index, tumour vascularity, thymidylate synthase (TS), vascular endothelial growth factor (VEGF)-A, VEGF-C, and E (epithelial)-cadherin. Concerning the survival of NSCLC patients, tumour vascularity (P<0.01), VEGF-A status (P=0.03), VEGF-C status (P=0.03), and E-cadherin status (P=0.03) were significant prognostic factors in patients with stage I NSCLCs. The Ki-67 proliferation index (P=0.02) and TS status (P<0.01) were significant prognostic factors in patients with stage II-III NSCLCs. In patients with stage II-III NSCLCs, furthermore, the survival of UFT (a combination of tegafur and uracil)-treated patients with TS-negative tumours was significantly better than those of any other patients. Biological markers associated with tumour angiogenesis or metastasis are useful for the detection of aggressive tumours among early-stage NSCLCs. Postoperative chemotherapy might be necessary in such tumours even in stage I. In contrast, tumour proliferation rate and TS status are useful markers for identifying less aggressive tumours in locally advanced NSCLCs. Thymidylate synthase expression is also a useful marker to evaluate responsiveness of UFT-based chemotherapy for these tumours.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / analysis*
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / immunology*
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Carcinoma, Non-Small-Cell Lung / surgery
  • Cell Proliferation
  • Female
  • Growth Substances / analysis
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / analysis
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / surgery
  • Male
  • Middle Aged
  • Neoplasm Staging / methods*
  • Neovascularization, Pathologic
  • Patient Care Planning
  • Predictive Value of Tests
  • Prognosis
  • Retrospective Studies
  • Sensitivity and Specificity
  • Thymidylate Synthase / analysis

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Growth Substances
  • Ki-67 Antigen
  • Thymidylate Synthase