Expression of the hepatocyte growth factor/c-Met pathway is increased at the cancer front in breast carcinoma

Pathol Int. 2001 Mar;51(3):172-8. doi: 10.1046/j.1440-1827.2001.01182.x.


Expression of hepatocyte growth factor (HGF) and c-Met (HGF receptor) has been reported in many neoplasms. We investigated coexpression of HGF and c-Met to determine the role of the HGF/c-Met pathway in breast carcinoma, especially at the cancer front. Eighty-eight cases of carcinoma of the breast were studied by immunohistochemistry and by in situ hybridization for HGF and c-Met expression. The staining pattern was termed "front accentuation pattern" when it was most conspicuous at the cancer front. HGF and c-Met proteins were expressed in cancer and stromal cells, with autocrine and paracrine patterns. The front accentuation pattern of c-Met was observed in cancer cells, but not in stromal cells. The front accentuation pattern was not observed in HGF. Coexpression of HGF and c-Met at the cancer front was correlated with histologic grade, reduced patient survival and a high Ki-67 labeling index. Our findings suggest that the HGF/c-Met pathway acts primarily as a mitogen, especially at the cancer front, in a paracrine manner and affects some clinical factors, including patient survival.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Carcinoma, Ductal, Breast / genetics
  • Carcinoma, Ductal, Breast / metabolism*
  • Carcinoma, Ductal, Breast / mortality
  • Carcinoma, Ductal, Breast / secondary
  • DNA, Neoplasm / analysis
  • Female
  • Hepatocyte Growth Factor / biosynthesis*
  • Hepatocyte Growth Factor / genetics
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Ki-67 Antigen / analysis
  • Lymph Nodes / pathology
  • Lymphatic Metastasis
  • Middle Aged
  • Neoplasm Staging
  • Proto-Oncogene Proteins c-met / biosynthesis*
  • Proto-Oncogene Proteins c-met / genetics
  • RNA, Messenger / metabolism
  • Survival Rate


  • DNA, Neoplasm
  • Ki-67 Antigen
  • RNA, Messenger
  • Hepatocyte Growth Factor
  • Proto-Oncogene Proteins c-met