ALTERED EXPRESSION OF RET PROTOONCOGENE PRODUCT IN PROSTATIC INTRAEPITHELIAL NEOPLASIA AND PROSTATE-CANCER

Background: The RET proto-oncogene encodes a protein that belongs to t he tyrosine kinase growth factor receptor family, Germline point mutat ions in RET are found in individuals with multiple endocrine neoplasia (MEN) syndromes, and gene rearrangements have been reported in papill ary thyroid cancers, We recently identified transcripts of the RET pro to-oncogene in human prostate cancer xenografts and prostate cancer ce ll lines by means of reverse transcription-polymerase chain reaction a nalyses, The purpose of this study was to investigate Pet protein expr ession in human prostate tissue, Methods: Pet protein expression was e valuated immunohistochemically in formalin-fixed, paraffin-embedded wh ole-prostate sections, The prostate specimens were obtained from 30 pa tients with prostate cancer after radical prostatectomies, Ret protein expression was compared in tumor foci and benign prostatic tissue, Me dullary thyroid carcinoma tissue associated with an MEN syndrome and p apillary thyroid cancer tissue served as positive controls, Results: R et appeared to be overexpressed in high-grade (histopathologically adv anced) prostatic intraepithelial neoplasia (PIN) and prostate cancer w hen compared with its expression level in benign prostatic secretory e pithelium. In addition, there was an apparent increase in Pet protein expression with decreased cellular differentiation, i.e., increasing G leason pattern, Conclusion: Expression of the RET protooncogene in ben ign prostatic epithelium, high-grade PIN, and histopathologically adva nced prostate cancer suggests that RET may play a role in the growth o f both benign and neoplastic prostate epithelial cells.