CXXC5 expression in prostate cancer: implications for cancer progression

Identification of genes specifically deregulated in prostate adenocarcinoma may lead to discovery of new oncogenes/tumour suppressors with clinical relevance for diagnosis, prognosis and/or therapy. CXXC5 is a gene encoding a retinoid-inducible nuclear factor, whose overexpression in breast tumours, metastatic malignant melanomas and papillary thyroid carcinoma has been recently reported. We previously found differential expression of CXXC5 transcripts in metastatic prostate cancer cell lines of both rat and human origin. However, knowledge on the expression of this gene in benign or malignant human prostate tissue is lacking. The aim of this study was to determine the mRNA and protein expression pattern of CXXC5 in human benign prostate tissue, proliferative inflammatory atrophy, high-grade prostatic intra-epithelial neoplasia and prostate cancer, using qPCR, chromogenic in situ hybridization and immunohistochemistry. Our results showed that protein levels determined by immunohistochemistry were in agreement with transcript levels observed by chromogenic in situ hybridization. CXXC5 mRNA and protein expressions were significantly higher in prostate cancer, high-grade prostatic intra-epithelial neoplasia, and proliferative inflammatory atrophy, compared to benign prostate tissue. Significantly, within the same tissue specimens, CXXC5 staining was stronger in malignant acini than in matched adjacent, benign acini; immunostaining for this protein was mainly localized to the nucleus of benign epithelial cells and both the nucleus and cytoplasm of malignant epithelial cells. Our findings suggest that CXXC5 may play a role in the process of prostate carcinogenesis. Additional studies are required to determine the biological and clinical significance of CXXC5 in prostate cancer development and/or progression.