Altered expression of RET proto-oncogene product in prostatic intraepithelial neoplasia and prostate cancer.
BACKGROUND
The RET proto-oncogene encodes a protein that belongs to the tyrosine kinase growth factor receptor family. Germline point mutations in RET are found in individuals with multiple endocrine neoplasia (MEN) syndromes, and gene rearrangements have been reported in papillary thyroid cancers. We recently identified transcripts of the RET proto-oncogene in human prostate cancer xenografts and prostate cancer cell lines by means of reverse transcription-polymerase chain reaction analyses. The purpose of this study was to investigate Ret protein expression in human prostate tissue.


METHODS
Ret protein expression was evaluated immunohistochemically in formalin-fixed, paraffin-embedded whole-prostate sections. The prostate specimens were obtained from 30 patients with prostate cancer after radical prostatectomies. Ret protein expression was compared in tumor foci and benign prostatic tissue. Medullary thyroid carcinoma tissue associated with an MEN syndrome and papillary thyroid cancer tissue served as positive controls.


RESULTS
Ret appeared to be overexpressed in high-grade (histopathologically advanced) prostatic intraepithelial neoplasia (PIN) and prostate cancer when compared with its expression level in benign prostatic secretory epithelium. In addition, there was an apparent increase in Ret protein expression with decreased cellular differentiation, i.e., increasing Gleason pattern.


CONCLUSIONS
Expression of the RET proto-oncogene in benign prostatic epithelium, high-grade PIN, and histopathologically advanced prostate cancer suggests that RET may play a role in the growth of both benign and neoplastic prostate epithelial cells.
Dawson
D M
DM
Department of Pathology, Case Western Reserve University Medical Center, Cleveland, OH 44106, USA.
Lawrence
E G
EG
MacLennan
G T
GT
Amini
S B
SB
Kung
H J
HJ
Robinson
D
D
Resnick
M I
MI
Kursh
E D
ED
Pretlow
T P
TP
Pretlow
T G
TG
D029721:Drosophila Proteins; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D011468:Prostatectomy; D019048:Prostatic Intraepithelial Neoplasia / Q000737:chemistry* / Q000473:pathology / Q000601:surgery; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000473:pathology / Q000601:surgery; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis*; D013964:Thyroid Neoplasms / Q000737:chemistry
D029721:Drosophila Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila