c-met proto-oncogene expression in benign and malignant human prostate tissues

J Urol. 1995 Jul;154(1):293-8.

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%) 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Bone Marrow / metabolism
  • Bone Neoplasms / genetics
  • Bone Neoplasms / secondary
  • Epithelium / metabolism
  • Epithelium / pathology
  • Gene Expression Regulation, Neoplastic*
  • Hepatocyte Growth Factor / genetics*
  • Humans
  • Lymphatic Metastasis / genetics
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Prostate / metabolism
  • Prostate / pathology
  • Prostatic Hyperplasia / genetics
  • Prostatic Hyperplasia / metabolism
  • Prostatic Hyperplasia / pathology
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins c-met
  • Receptor Protein-Tyrosine Kinases / genetics*

Substances

  • Proto-Oncogene Proteins
  • Hepatocyte Growth Factor
  • Proto-Oncogene Proteins c-met
  • Receptor Protein-Tyrosine Kinases