C-met Proto-Oncogene Expression in Benign and Malignant Human Prostate Tissues

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Abstract
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 percent) of high grade prostatic intraepithelial neoplasia (PIN). Overall, c-met protein staining was noted in 36 of 43 (84 percent) primary prostate cancer samples versus 2 of 11 (18 percent) benign prostate hyperplasia samples (p less than 0.0001) and in 4 of 4 (100 percent) lymph node metastases, 23 of 23 (100 percent) bone marrow metastases and 1 of 3 (33 percent) other metastatic sites. There was a clear relationship between c-met protein staining and higher grade adenocarcinomas (p less than 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.