Clinical Cancer Research Bridging the Lab and the Clinic in Cancer Medicine Translational Cancer Medicine 2008: Cancer Clinical Trials and Personalized Medicine
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Clinical Cancer Research Vol. 11, 993-999, February 2005
© 2005 American Association for Cancer Research


Human Cancer Biology

Expression of Erythropoietin and Erythropoietin Receptor in Non–Small Cell Lung Carcinomas

Koami Dagnon1, Emilie Pacary3, Frédéric Commo2, Martine Antoine2, Myriam Bernaudin3, Jean-Francois Bernaudin1 and Patrice Callard2

1 Service d'Histologie-Biologie Tumorale and 2 Service d'Anatomie Pathologique, Unité Propre de Recherche de l'Enseignement Supérieur EA 3499, Université Paris 6, Hôpital Tenon, Paris, France and 3 Unité Mixte de Recherche-Centre National de la Recherche Scientifique 6185, Université de Caen, Caen, France

Requests for reprints: Patrice Callard, Service d'Anatomie-Pathologique and Unité Propre de Recherche de l'Enseignement Supé rieur EA 3499, Université Paris 6, Hôpital Tenon, 4 rue de la Chine, 75970 Paris cedex 20, France. Phone: 33-1-56-01-70-13; Fax: 33-1-56-01-78-76; E-mail: patrice.callard{at}tnn.ap-hop-paris.fr.

Purpose: Expression of erythropoietin (Epo) and its receptor (Epo-R) has been shown in various normal and neoplastic nonhematopoietic tissues. This study, in non–small cell lung carcinoma, was designed to investigate the previously unreported expression of Epo and Epo-R as well as hypoxia-inducible factor-1{alpha} (HIF-1{alpha}), which is known to control Epo expression.

Experimental Design: Samples from lung squamous cell carcinomas (n = 17) and adenocarcinomas (n = 12) were obtained from patients undergoing curative surgery. mRNA transcripts of Epo, Epo-R, soluble Epo-R (sEpo-R), HIF-1{alpha}, and factor inhibiting HIF-1 (FIH-1) were evaluated by reverse transcription-PCR, whereas localization of Epo, Epo-R, and HIF-1{alpha} was assessed by immunohistochemistry.

Results: Epo, Epo-R, sEpo-R, HIF-1{alpha}, and FIH-1 transcripts were detected by reverse transcription-PCR in all samples tested, but with heterogeneous levels of expression for Epo, Epo-R, and sEpo-R. Coordinated levels of mRNA were observed for HIF-1{alpha} and FIH-1.

Epo was detected in carcinomatous cells by immunohistochemistry in 50% of samples and Epo-R was detected in 96% of samples. Co-expression of Epo and Epo-R was observed on contiguous sections from 50% of tumors. HIF-1{alpha} was immunolocalized in 80% of non–small cell lung carcinomas.

Conclusion: Epo-R was expressed in almost all samples and Epo was expressed in one half of samples on immunohistochemistry and in 100% of samples by mRNA detection, suggesting a potential paracrine and/or autocrine role of endogenous Epo in non–small cell lung carcinoma. The detection of stabilized HIF-1{alpha} suggests a possible role in Epo expression. Moreover, in the light of these results, the potential interactions between therapeutic recombinant Epo and the putative neoplastic Epo/Epo-R signaling pathways must be considered.




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Copyright © 2005 by the American Association for Cancer Research.