ORIGINAL PAPER EPO-R Expression Patterns in Resected Gastric Adenocarcinoma Followed by Adjuvant Chemoradiation Treatment Maria Sereno & Javier De castro & Cristóbal Belda-Iniesta & Miguel Angel Garcia-Cabezas & Paloma Cejas & Enrique Casado & Jorge Barriuso & Jaime Feliu & Javier Larrauri Received: 1 August 2008 / Accepted: 16 October 2008 / Published online: 11 November 2008 # Arányi Lajos Foundation 2008 Abstract The primary aim was to determine whether Epo- R immunohistochemical expression is related to disease free survival (DFS) in specimens of GC from patients who underwent adjuvant chemoradiation. Specimens of gastric adenocarcinomas obtained from 44 patients who had undergone curative gastrectomy and adjuvant treatment were investigated immunohistochemically expression of Epo-R. Three patterns for Epo-R staining were defined: Pattern A (secretory cells-like staining), Pattern B (parietal- like staining) and Pattern C (chief-like staining). Median DFS was 38 months (CI 95%: 33–43) and 15 months (IC 95%: 3–27) in the pattern B and C, respectively, but it was not reached in the pattern A (p= 0.06). Our findings suggest that there may be a relationship between Epo-R expression and DFS in the patients with GC resected. Keywords Gastric cancer . Epo-R . adjuvant chemoradiation Introduction Erythropoietin (Epo) is a glycoprotein hormone responsible for regulating the erythropoiesis [1]. Epo normally is produced by the kidney and liver in adults. Its gene expression is modulated by tissue hypoxia [2]. Epo acts by binding to Epo-specific receptors (Epo-R), which belong to the citokine receptor type I superfamily. EpoR stimula- tion in erythroblasts promotes proliferation and differenti- ation, leads to increased expression of the antiapoptotic proteins Bcl-2 and Bcl-Xl, and inhibits the apoptosis [3]. Epo-R is expressed by a variety of cell types as well, including endothelial cells, neurons [4], mammary epithelial cells [5], and human endometrial cells suggesting a wider biologic role for Epo signalling unrelated to erythropoiesis. Epo also stimulates proliferation and migration of human endothelial cells and promotes angiogenesis. Major signal- transduction pathways activated by Epo include the Jak/ signal transducer and activator of transduction (STAT) and Ras/mitogen-activated protein kinase pathways, which are involved in the inhibition of apoptosis and the stimulation of cell proliferation in response to this hormone [6, 7]. Previous studies have shown that cultured human breast and cervical carcinoma cells, as well as other carcinoma cells, express high levels of Epo/Epo-R and both mRNA and protein [6, 8]. These authors have demostrated that exposure of tumour cells transfected with Epo-R to recombinant human Epo (rHuEpo) stimulated tyrosine phosphorylation and subse- quent DNA synthesis and proliferation, suggesting that Epo signalling is biologically active in malignant cells [6, 7]. Recently, Mohyeldin has found a correlation between Epo and Epo-R expression and malignant progression in head and neck squamous cancer [9, 10]. Gastric cancer (GC) remains one of the leading causes of cancer related deaths worldwide. Many biological factors Pathol. Oncol. Res. (2009) 15:1–10 DOI 10.1007/s12253-008-9118-9 J. De castro : C. Belda-Iniesta : M. A. Garcia-Cabezas : P. Cejas : J. Barriuso : J. Feliu : J. Larrauri Medical Oncology Division, University Hospital La Paz, Madrid, Spain M. Sereno (*) : E. Casado Medical Oncology Division, Infanta Sofía Hospital, San Sebastian de los Reyes, Madrid, Spain e-mail: mariasereno@yahoo.es