Prognostic relevance of TTF-1 and MMP-9 expression in advanced lung adenocarcinoma

Lung Cancer. 2009 Apr;64(1):105-9. doi: 10.1016/j.lungcan.2008.07.017. Epub 2008 Sep 17.

Abstract

Background: The thyroid transcription factor-1 (TTF-1) is a tissue-specific transcription factor that could play an important role in cell differentiation and morphogenesis of lung tumors. Matrix metalloproteinase-9 (MMP-9) is a protease commonly expressed in non-small cell lung cancer, conferring angiogenic and metastatic potential.

Methods: We assessed TTF-1 and MMP-9 tumor expression by immunohistochemistry in 51 patients with lung adenocarcinoma, stage IIIB or IV, treated with platinum regimens. A bicategorical prognostic model was obtained using the Kaplan-Meier method, Cox regression, and conjunctive consolidation.

Results: The median expression of TTF-1 was 30.0% (range: 0-85.9%). All tumors expressed MMP-9 (median: 78.7%; range: 15.2-96.1%). Median survival was 41.6 weeks, with estimated 1- and 2-year survival rates of 45.0% and 22.0%, respectively. Poor performance status (Karnofsky scale) - hazards ratio (HR): 1.03, 95% confidence interval (CI): 1.01-1.06; low TTF-1 expression (<40%) - HR: 4.00, 95% CI: 1.75-9.09; and high MMP-9 expression (> or =80%) - HR: 2.82, 95% CI: 1.30-6.08 were independent prognostic factors. Patients could be stratified in three death risk groups according to markers expression: low risk (high TTF-1 and low MMP-9; median survival: 127.6 weeks), intermediate risk (low TTF-1 or high MMP-9; median survival: 39.0 weeks); and high risk (low TTF-1 and high MMP-9; median survival: 16.4 weeks).

Conclusion: TTF-1 and MMP-9 tumor expression as detected by immunohistochemistry may allow identification of different, clinically meaningful, prognostic groups of advanced lung adenocarcinoma patients treated with platinum regimens.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / secondary
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / metabolism
  • Biopsy
  • DNA-Binding Proteins / metabolism*
  • Female
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Male
  • Matrix Metalloproteinase 9 / metabolism*
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Survival Rate
  • Transcription Factors
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • DNA-Binding Proteins
  • TTF1 protein, human
  • Transcription Factors
  • Matrix Metalloproteinase 9