CPEB4 immunohistochemical expression is associated to prognosis in stage IV colorectal carcinoma

Abstract

The cytoplasmic polyadenylation element binding protein 4 (CPEB4) is a RNA binding protein and translational regulator. It has been associated with tumor growth, vascularization and invasion and with tumor progression in breast, pancreas and lung carcinomas. To the best of our knowledge only one previous report has analyzed the prognostic value of CPEB4 in an experimental model of colorectal carcinoma. We have reviewed the files of patients with stage IV colorectal carcinoma metastatic to the liver. All the patients had received chemotherapy followed by hepatic metastasis resection and subsequent resection of the colon (liver-first approach). We have gathered demographic, analytical and morphological data of the primary tumors. We have performed immunohistochemical analysis of CPEB4 expression in these tumors and analyzed the potential prognostic value of this protein. 50 patients fulfilled inclusion criteria for the present study. All of them received preoperative chemotherapy based on platinum and also postoperative chemotherapy, with or without targeted drugs (18% received anti-epidermal growth factor receptor (EGFR) drugs and 24% anti-vascular endothelial growth factor receptor (VEGFR) drugs. 66% of the primaries were of sigmoid-rectal origin. CPEB4 expression was mainly cytoplasmic and it was scored as intense in 46% of the patients. Survival analysis revealed a significant association between progression free survival (PFS) and overall survival (OS) and CPEB4 immunohistochemical expression, which was independent in the multivariate analysis. CPEB4 behaves as a significant predictor of prognosis in stage IV colorectal carcinoma. The existence of CPEB4 specific inhibitors can open a new way for targeted therapy. Larger prospective studies are needed to confirm our promising results.