Expression of Peroxisome Proliferator Activated Receptor-Gamma (PPAR-γ) in Human Non-Small Cell Lung Carcinoma: Correlation With Clinicopathological Parameters, Proliferation and Apoptosis Related Molecules and Patients' Survival

Pathol Oncol Res. 2012 Oct;18(4):875-83. doi: 10.1007/s12253-012-9517-9. Epub 2012 Mar 18.

Abstract

Peroxisome proliferator-activated receptor-γ (PPAR-γ) has currently been considered as molecular target for the treatment of human metabolic disorders. PPAR-γ has also been implicated in the pathogenesis and progression of several types of cancer, being associated with cell differentiation, growth and apoptosis. The present study aimed to evaluate the clinical significance of PPAR-γ expression in non-small cell lung carcinoma (NSCLC). PPAR-γ protein expression was assessed immunohistochemically in tumoral samples of 67 NSCLC patients and was statistically analyzed in relation to clinicopathological parameters, proliferation and apoptosis related molecules and patients' survival. Positive PPAR-γ expression was prominent in 30 (45 %) out of 67 NSCLC cases. PPAR-γ positivity was more frequently observed in squamous cell lung carcinoma cases compared to lung adenocarcinoma ones (p = 0.048). PPAR-γ positivity was significantly associated with bcl-2 positivity (p = 0.016) and borderline with c-myc positivity (p = 0.052), whereas non associations with grade of differentiation, TNM stage, Ki-67, p53, bax proteins' expression and patients' survival were noted. In the subgroup of squamous cell lung carcinoma cases, PPAR-γ positivity was significantly associated with tumor size (p = 0.038), while in lung adenocarcinoma ones with histopathological grade of differentiation (p = 0.026). The present study supported evidence for possible participation of PPAR-γ in the biological mechanisms underlying the carcinogenic evolution of the lung. Although the survival prediction using PPAR-γ expression as a marker seems uncertain, the observed correlation with apoptosis related proteins reinforces the potential utility of PPAR-γ ligands as cell cycle modulators in future therapeutic approaches in lung cancer.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis / physiology
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Cycle / physiology
  • Cell Growth Processes / physiology
  • Chi-Square Distribution
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • Male
  • Middle Aged
  • PPAR gamma / biosynthesis*
  • Survival Rate

Substances

  • PPAR gamma