Prostaglandin E Receptor EP4 expression, survival and pattern of recurrence in locally advanced NSCLC

• Published in: Lung cancer (Amsterdam, Netherlands) Netherlands), 2016-11, Vol.101, p.88-91
• Main Authors: Bhooshan, Neha, M.D., Ph.D, Staats, Paul N., M.D, Fultonts, Amy M., Ph.D, Feliciano, Josephine L., M.D, Edelman, Martin J., M.D
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; COX-2; Cyclooxygenase 2 - metabolism; EP4 receptor; Female; Hematology, Oncology and Palliative Medicine; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Nonsmall cell lung cancer; Prognosis; Pulmonary/Respiratory; Receptors, Prostaglandin E, EP4 Subtype - metabolism; Stage 3; Survival Analysis; Treatment
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/j.lungcan.2016.09.011

Abstract Background 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 PGE2 induces 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 + ). Methods 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. Results EP4 nuclear staining 0-1 vs. 2+ was associated with overall survival, (OS) (44.3 vs. 18 mo; HR = .41, p = .024) and numerically superior progression free survival (PFS) (16.4 vs. 10.2 mo, p =.16). EP4 cytoplasmic staining did not correlate with OS (0-1 vs 2+, 23.8 vs 28.8 mo; HR = 1.2, p = .81). Relapse pattern (no relapse or local vs. systemic) did not correlate with EP nuclear staining (p = 1.0, X2 ). Conclusions 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.