Tissue microarray analysis of hepatocyte growth factor/Met pathway components reveals a role for Met, matriptase, and hepatocyte growth factor activator inhibitor 1 in the progression of node-negative breast cancer

Cancer Res. 2003 Mar 1;63(5):1101-5.

Abstract

Numerous studies have demonstrated that overexpression of Met, the hepatocyte growth factor(HGF) receptor, plays an important role in tumorigenesis. Met activation can either occur through ligand-independent or -dependent mechanisms, both of which are mediated by a series of proteases and modulators. We studied the protein expression of several components of the HGF/Met pathway on a cohort of 330 node-negative breast carcinomas using a tissue microarray annotated with 30-year, disease-specific patient follow-up data. We examined HGF, matriptase (an activator of HGF expressed on mammary epithelial cell surfaces), HAI-I (the cognate inhibitor of matriptase), and the Met receptor itself. Our studies demonstrate tight correlation between the expression of HGF, matriptase, and Met in breast carcinoma. High-level expression of Met, matriptase, and HAI-I were associated with poor patient outcome. Met and HAI-I showed independent prognostic value when compared with traditional breast markers in a multivariate analysis. Intriguingly, antibodies against the intracellular but not the extracellular domain of Met were prognostic, suggesting that overexpression of the cytoplasmic-tail of Met, perhaps through cleavage or truncating mutation, may play an important role in breast cancer progression.

Publication types

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

MeSH terms

  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Hepatocyte Growth Factor / biosynthesis*
  • Hepatocyte Growth Factor / metabolism
  • Humans
  • Membrane Glycoproteins / biosynthesis*
  • Prognosis
  • Proteinase Inhibitory Proteins, Secretory
  • Proto-Oncogene Proteins c-met
  • Proto-Oncogene Proteins*
  • Receptors, Growth Factor*
  • Serine Endopeptidases / biosynthesis*
  • Trans-Activators / biosynthesis*
  • Trypsin / biosynthesis*

Substances

  • Membrane Glycoproteins
  • Proteinase Inhibitory Proteins, Secretory
  • Proto-Oncogene Proteins
  • Receptors, Growth Factor
  • SPINT1 protein, human
  • Trans-Activators
  • Hepatocyte Growth Factor
  • MET protein, human
  • Proto-Oncogene Proteins c-met
  • Serine Endopeptidases
  • matriptase
  • ST14 protein, human
  • Trypsin