C-Met overexpression in node-positive breast cancer identifies patients with poor clinical outcome independent of Her2/neu

Int J Cancer. 2005 Feb 10;113(4):678-82. doi: 10.1002/ijc.20598.

Abstract

Receptor tyrosine kinases play an important role in malignant transformation of epithelial cells by activating signal transduction pathways important for proliferation, invasion and metastasis. In a pilot study (n = 40), we evaluated expression of the c-Met and Her2/neu receptor tyrosine kinases and the c-Met ligand hepatocyte growth factor/scatter factor (HGF/SF) in primary breast cancers and their lymph node metastases using both conventional immunohistochemistry and confocal immunofluorescence. Neither c-Met and HGF/SF nor Her2/neu expression correlated with established prognostic factors such as age, lymph node involvement, estrogen receptor (ER), progesterone receptor (PR), tumor size, or grade. Both staining methods confirmed a significant correlation between c-Met overexpression and a high risk of disease progression. Furthermore, among tumors with c-Met overexpression, only 50% also overexpress Her2/neu, thus identifying a subset of patients with aggressive disease in addition to Her2/neu. Median disease-free survival in patients with c-Met overexpressing tumors was 8 months compared to 53 months when c-Met expression was low (p = 0.037; RR = 3.0). This significant impact of c-Met on tumor aggressiveness independent of Her2/neu was also confirmed by multivariate analysis. In conclusion, the role of c-Met expression as a prognostic variable and consequently as an interesting target for novel therapeutic approaches deserves further analysis in a larger cohort of patients.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Disease Progression
  • Disease-Free Survival
  • Female
  • Fibrocystic Breast Disease / drug therapy
  • Fibrocystic Breast Disease / metabolism
  • Fibrocystic Breast Disease / pathology
  • Hepatocyte Growth Factor / metabolism
  • Humans
  • Hyperplasia / drug therapy
  • Hyperplasia / metabolism
  • Hyperplasia / pathology
  • Ligands
  • Lymph Nodes / pathology
  • Lymphatic Metastasis / pathology*
  • Middle Aged
  • Neoplasm Staging
  • Pilot Projects
  • Proto-Oncogene Proteins c-met / metabolism*
  • Receptor, ErbB-2 / metabolism*
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Risk Factors
  • Survival Rate
  • Treatment Outcome

Substances

  • Ligands
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Hepatocyte Growth Factor
  • Proto-Oncogene Proteins c-met
  • Receptor, ErbB-2