title: Prostaglandin E Receptor EP4 expression, survival and pattern of recurrence in locally advanced NSCLC.
abstract: Elevated COX-2 expression has been correlated with inferior outcome in NSCLC. COX-2 catalyzes the transformation of arachidonate to PGE2. We and others have demonstrated that PGE2induces proliferation and metastatic spread and immunosuppression through the G protein-coupled EP4 receptor. We hypothesized that EP4 expression on malignant cells would correlate with outcome and patterns of relapse after treatment of LANSCLC stage IIIA (7th edition, N2+).
  
  
  
  Tissue specimens from 41 pts treated for LANSC at UMGCC were obtained. A tissue microarray was prepared and examined for EP4 expression. Intensity of staining was scored semi-quantitatively as 0-4 in both the nuclear and cytoplasmic compartments by a pathologist blinded to the clinical data.
  
  
  
  EP4 nuclear staining 0-1 vs. 2+ was associated with overall survival, (OS) (44.3 vs. 18 mo; HR=0.41, p=0.024) and numerically superior progression free survival (PFS) (16.4 vs. 10.2 mo, p=0.16). EP4 cytoplasmic staining did not correlate with OS (0-1 vs. 2+, 23.8 vs. 28.8 mo; HR=1.2, p=0.81). Relapse pattern (no relapse or local vs. systemic) did not correlate with EP nuclear staining (p=1.0, X2).
  
  
  
  This is the first clinical study of EP4 expression in lung cancer. There was a significant correlation between OS and nuclear EP4 expression, indicating that this is a potential therapeutic target. Studies with AT-007, a specific inhibitor of EP4, are planned to commence this year.
authors: University of Maryland Marlene and Stewart Greenebaum Cancer Center, 22 South Greene Street, Baltimore, MD, 21201, USA.
authors: Neha
authors: N
authors: Bhooshan
authors: University of Maryland Marlene and Stewart Greenebaum Cancer Center, 22 South Greene Street, Baltimore, MD, 21201, USA.
authors: Paul N
authors: PN
authors: Staats
authors: University of Maryland Marlene and Stewart Greenebaum Cancer Center, 22 South Greene Street, Baltimore, MD, 21201, USA; Baltimore Veterans Administration Medical Center, Baltimore, MD 21201, USA.
authors: Amy M
authors: AM
authors: Fulton
authors: University of Maryland Marlene and Stewart Greenebaum Cancer Center, 22 South Greene Street, Baltimore, MD, 21201, USA.
authors: Josephine L
authors: JL
authors: Feliciano
authors: University of Maryland Marlene and Stewart Greenebaum Cancer Center, 22 South Greene Street, Baltimore, MD, 21201, USA. Electronic address: medelman@umm.edu.
authors: Martin J
authors: MJ
authors: Edelman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005260:Female; D006801:Humans; D008175:Lung Neoplasms; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D011379:Prognosis; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000378:metabolism*; D016019:Survival Analysis
chemical_list: D058309:Receptors, Prostaglandin E, EP4 Subtype; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human
keywords: COX-2; EP4 receptor; Nonsmall cell lung cancer; Prognosis; Stage 3; Treatment