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Erythropoietin and Erythropoietin Receptor Coexpression Is Associated with Poor Survival in Stage I Non–Small Cell Lung Cancer

Authors' Affiliations: ¹ Service d'Oncologie Médicale, Hôpital Avicenne, Assistance Publique-Hôpitaux de Paris, Université Paris 13; ² Centre de Recherche en Nutrition Humaine Ile-de-France, UMR INSERM/INRA/CNAM, SMBH Paris 13; ³ Département Interhospitalier de Santé Publique, Hôpital Avicenne, Assistance Publique-Hôpitaux de Paris, Bobigny, Paris; ⁴ Service d'Histologie Biologie Tumorale, EA 3499 Université Pierre et Marie Curie Paris, Université Paris 6, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris; ⁵ Service d'Anatomie et Cytologie Pathologiques, EA3499 Université Pierre et Marie Curie Paris, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris; ⁶ Institut Mutualiste Montsouris, Département Thoracique; ⁷ Institut Mutualiste Montsouris, Service d'Anatomie Pathologique, Paris, France; and ⁸ Département de Médecine, Institut Gustave Roussy, Villejuif, Paris

Requests for reprints: Pierre Saintigny, Service d'Oncologie Médicale, Hôpital Avicenne, 125 Route de Stalingrad, 93009 Bobigny, France. Phone: 33-1-48-95-50-32; Fax: 33-1-48-95-50-35/33-1-48-95-50-30; E-mail: pierre.saintigny{at}avc.aphp.fr.

Purpose: This study was designed to evaluate the prognostic effect of erythropoietin (EPO) and EPO receptor (EPO-R) expression in stage I non–small cell lung cancer (NSCLC) patients.

Experimental Design: EPO and EPO-R expression in 158 tumor samples from resected stage I NSCLC was evaluated using immunohistochemistry and tissue array technology.

Results: EPO-R and EPO were highly expressed in 20.9% and 35.4% of tumors, respectively. High EPO-R expression compared with negative or low-level expression was associated with a poor 5-year disease-specific survival (60.6% versus 80.8%; P = 0.01, log-rank test). High EPO expression compared with negative and low-level expression was associated with a trend toward a poor 5-year disease-specific survival (69.6% versus 80.4%; P = 0.13, log-rank test). A high level of EPO-R and EPO coexpression was associated with a poor 5-year disease-specific survival compared with other groups of patients (50.0% versus 80.0% survival at the end of follow-up; P = 0.005, log-rank test). In multivariate analysis for disease-specific survival, high-level EPO-R and EPO coexpression was an independent prognostic factor for disease-specific survival (hazard ratio, 2.214; 95% confidence interval, 1.012-4.848; P = 0.046).

Conclusion: These results establish the pejorative prognostic value of EPO and EPO-R expression in early-stage resected NSCLC and suggest a potential paracrine and/or autocrine role of endogenous EPO in NSCLC aggressiveness.

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