Abstract

ABSTRACT Background Ephrin receptors (Ephs) 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 EphA4 expression in lung cancer. Material and methods 101 patients who underwent surgical resection due to lung cancer were participated in this study. None of them received any kind of treatment prior to surgery. 86 were men and 15 women with a mean age of 62 years old. The tumors were classified histologically as adenocarcinoma in 48, squamous cell carcinoma in 33, large cell carcinoma in 11 and small cell carcinoma in 9 cases. Using tissue microarray technology, 101 paraffin-embedded tissue samples were cored, re-embedded to the final recipient block and used for EphA4 protein immunohistochemical expression. All analyses were performed by SPSS for Windows Software (SPSS Inc, Chicago, IL, USA) and a p value less than 0.05 was considered the limit of statistical significance. Results EphA4 positivity was noted in 36 out of 101 (36%) cases. EphA4 staining intensity was classified as mild in 11 (31%), moderate in 23 (64%) and intense in 2 (5%) out of 36 positive cases. Increased EphA4 positivity and moderate/intense EphA4 staining intensity were noted in adenocarcinoma and squamous cell lung carcinoma cases compared to large cell and neuroendocrine carcinoma ones (p = 0.0049 and p = 0.0170, respectively). EphA4 positivity and staining intensity were associated with the presence of lymph node metastases (p = 0.0349 and p = 0.0404, respectively). EphA4 staining intensity was also correlated with tumor histopathological stage (p = 0.0145). No association of EphA4 positivity nor staining intensity were noted with tumor histopathological grade, size and organ metastasis. Conclusions The current study supports evidence for possible EphA4 participation in lung cancer biological behaviour, implying also its potent role as a therapeutic target. However, further molecular and clinical studies are required in order to define the significance of Ephs and their ligands (ephs) in lung cancer prognosis and management. Disclosure All authors have declared no conflicts of interest.

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