Clinical implications of microsomal prostaglandin e synthase-1 overexpression in human non-small-cell lung cancer

Ann Surg Oncol. 2006 Sep;13(9):1224-34. doi: 10.1245/s10434-006-9001-4. Epub 2006 Sep 3.

Abstract

Background: Microsomal prostaglandin E synthase-1 (mPGES-1) has recently been found to overexpress in human cancers, including non-small-cell lung cancer (NSCLC). However, the clinical value is largely unknown. The aim of this study was to investigate the associations between mPGES-1 expression in NSCLC and the clinical characteristics and survival outcome.

Methods: Between 2001 and 2003, paired fresh tumorous and nontumorous samples were prospectively procured from patients undergoing surgery for NSCLC. The expression of mPGES-1 was assessed by using Western blot in 93 subjects and reverse transcriptase-polymerase chain reaction in 35. Overexpression of mPGES-1 was defined as a more than 2-fold expression in the tumorous sample compared with the corresponding nontumorous one. Immunohistochemistry was used to confirm its localization to the tumor cells. In a subset of 30 cases, cyclooxygenase-2 (COX-2) was also analyzed to assess its association with mPGES-1.

Results: The protein and messenger RNA of mPGES-1 were both expressed at higher levels in the tumor samples (P < .001 and P = .006, respectively). The expressions of mPGES-1 and COX-2 were unrelated (P = .715). Overexpression of mPGES-1 protein was observed in 61 (65.6%) of 93 patients, but it was not significantly associated with the clinicopathologic characteristics or overall and disease-free survivals. However, mPGES-1 overexpression seemed to be associated with the likelihood of subsequent pulmonary metastases and a lower tendency for developing bony metastases (P = .001 and P = .006, respectively).

Conclusions: Our results demonstrated that mPGES-1 was overexpressed in NSCLC, unassociated with COX-2. Overexpression of mPGES-1 per se was not a prognostic indicator, but it might be implicated in the organ preference of metastasis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / enzymology
  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Blotting, Western
  • Carcinoma, Large Cell / enzymology
  • Carcinoma, Large Cell / genetics
  • Carcinoma, Large Cell / pathology
  • Carcinoma, Non-Small-Cell Lung / enzymology*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Squamous Cell / enzymology
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology
  • Cyclooxygenase 2 / metabolism
  • Female
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunoblotting
  • Immunoenzyme Techniques
  • Intramolecular Oxidoreductases / genetics
  • Intramolecular Oxidoreductases / metabolism*
  • Lung Neoplasms / enzymology*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Male
  • Membrane Proteins / metabolism
  • Middle Aged
  • Prostaglandin-E Synthases
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured

Substances

  • Membrane Proteins
  • RNA, Messenger
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Intramolecular Oxidoreductases
  • PTGES protein, human
  • Prostaglandin-E Synthases