c-met proto-oncogene expression in benign and malignant human prostate tissues.
Previously, we demonstrated that hepatocyte growth factor/scatter factor (HGF/SF) is expressed by human bone stromal cells and is a powerful mitogen to prostatic epithelial cells in culture. Based on these observations, we hypothesized that, if prostate cancer cells in the prostate or bone environment respond to HGF/SF as a mitogen, then they must express the HGF/SF receptor, which is coded by the c-met proto-oncogene. We used immunohistochemical techniques to: 1) assess the presence and localization of c-met protein in benign and malignant human prostate tissues and 2) correlate the presence of c-met protein with tumor stage, grade and androgen sensitivity. c-met protein immunostaining was consistently observed in the basal epithelial layer of normal prostate glands but was absent in luminal epithelial cells of the peripheral and transition zones. c-met protein immunostaining was detected in 10 of 11 foci (91%) of high grade prostatic intraepithelial neoplasia (PIN). Overall, c-met protein staining was noted in 36 of 43 (84%) primary prostate cancer samples versus 2 of 11 (18%) benign prostate hyperplasia samples (p < 0.0001) and in 4 of 4 (100%) lymph node metastases, 23 of 23 (100%) bone marrow metastases and 1 of 3 (33%) other metastatic sites. There was a clear relationship between c-met protein staining and higher grade adenocarcinomas (p < 0.001). c-met protein is frequently detected in PIN and higher grade prostate cancers; future studies should evaluate the biological significance of these findings.
Pisters
L L
LL
Department of Urology, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Troncoso
P
P
Zhau
H E
HE
Li
W
W
von Eschenbach
A C
AC
Chung
L W
LW
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000378:metabolism; D001859:Bone Neoplasms / Q000235:genetics / Q000556:secondary; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases