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Ephrin (Eph) receptor A1, A4, A5 and A7 expression in human non-small cell lung carcinoma: associations with clinicopathological parameters, tumor proliferative capacity and patients’ survival

Constantinos Giaginis12, Nikolaos Tsoukalas3, Evangelos Bournakis3, Paraskevi Alexandrou1, Nikolaos Kavantzas1, Efstratios Patsouris1 and Stamatios Theocharis1*

Author Affiliations

1 First Department of Pathology, Medical School, National and Kapodistrian University of Athens, 75 M. Asias str., Goudi, Athens GR11527, Greece

2 Department of Food Science and Nutrition, School of the Environment, University of the Aegean, Myrina Lemnos, Greece

3 Department of Medical Oncology, 401 General Military Hospital, Athens, Greece

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BMC Clinical Pathology 2014, 14:8  doi:10.1186/1472-6890-14-8

Published: 4 February 2014



Ephrin (Eph) receptors are frequently overexpressed in a wide variety of human malignant tumors, being associated with tumor growth, invasion, metastasis and angiogenesis. The present study aimed to evaluate the clinical significance of EphA1, A4, A5 and A7 protein expression in non-small cell lung carcinoma (NSCLC).


EphA1, A4, A5 and A7 protein expression was assessed immunohistochemically in tissue microarrays of 88 surgically resected NSCLC and was analyzed in relation with clinicopathological characteristics and patients’ survival.


Elevated EphA4 expression was significantly associated with low histopathological stage and presence of inflammation (p = 0.047 and p = 0.026, respectively). Elevated EphA7 expression was significantly associated with older patients’ age, presence of fibrosis and smaller tumor size (p = 0.036, p = 0.029 and p = 0.018, respectively). EphA1, A5 and A7 expression were positively associated with tumor proliferative capacity (p = 0.047, p = 0.002 and p = 0.046, respectively). Elevated EphA4, A5 and A7 expression were identified as predictors of favourable patients’ survival at both univariate (Log-rank test, 0 = 0.019, p = 0.006 and p = 0.012, respectively) and multivariate levels (Cox-regression analysis, p = 0.029, p = 0.068 and p = 0.044, respectively).


The present study supported evidence that Ephs may be involved in lung cancer progression, reinforcing their utility as clinical biomarkers for patients’ management and prognosis, as also as potential targets for future therapeutic interventions.

Ephrin receptors; Non-small cell lung carcinoma; Clinicopathological parameters; Prognosis; Immunohistochemistry