Clinical implications of microsomal prostaglandin e synthase-1 overexpression in human non-small-cell lung cancer.
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.
Wang
Hao-Wei
HW
Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital and School of Medicine, National Yang-Ming University, 201, Sec 2, Shih-Pai Road, Taipei 112, Taiwan.
Hsueh
Chung-Tsen
CT
Lin
Chien-Fu Jeff
CF
Chou
Teh-Ying
TY
Hsu
Wen-Hu
WH
Wang
Liang-Shun
LS
Wu
Yu-Chung
YC
D000230:Adenocarcinoma / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D018287:Carcinoma, Large Cell / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015151:Immunoblotting; D007124:Immunoenzyme Techniques; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D000071876:Prostaglandin-E Synthases; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D008565:Membrane Proteins; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases