Met expression is associated with poor outcome in patients with axillary lymph node negative breast carcinoma

Cancer. 1999 Dec 1;86(11):2259-65. doi: 10.1002/(sici)1097-0142(19991201)86:11<2259::aid-cncr13>;2-2.


Background: Activation of Met, the receptor for scatter factor/hepatocyte growth factor, is associated with mitogenesis, motogenesis, and decreased cell adhesion. Elevated expression of Met has been shown in advanced cases of carcinoma of the prostate, stomach, pancreas, and thyroid. The authors previously demonstrated that Met expression is an independent prognostic marker associated with decreased survival in patients with breast carcinoma.

Methods: Expression of Met in 113 archival breast carcinoma specimens from patients with axillary lymph node negative invasive ductal carcinoma was evaluated using a standard immunoperoxidase technique. Cases were scored by two pathologists using an H-score algorithm and then analyzed for correlation with known prognostic factors and survival.

Results: Expression of Met showed a bimodal distribution with 25% of cases showing high levels of expression. In contrast to previous studies, the results of the current study showed a significant association between Met expression and nuclear and histologic grade. The 5-year survival rate for Met negative patients with tumors with low Met expression was 95% in this cohort, compared with 80% for patients with tumors showing high Met expression. Patients whose tumors had a high level of Met expression were found to have a 5-year relative risk (RR) of dying of metastatic disease of 5.05 (P = 0.03) independent of patient age and tumor size. Combined analysis of Met and nuclear grade resulted in a marked increase in independent predictive value (RR = 33.4; P < 0.01).

Conclusions: The results of the current study found that high levels of Met expression were associated with death due to metastatic disease in patients with axillary lymph node negative breast carcinoma. Expression of Met may be a useful prognostic indicator of more aggressive disease in patients whose prognosis is not easily stratified by current histopathologic markers.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Axilla
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Carcinoma / genetics*
  • Carcinoma / pathology
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Hepatocyte Growth Factor / biosynthesis
  • Humans
  • Immunohistochemistry
  • Lymph Nodes / pathology*
  • Lymphatic Metastasis
  • Middle Aged
  • Neoplasm Staging
  • Prognosis
  • Proto-Oncogene Proteins c-met / biosynthesis*


  • Biomarkers, Tumor
  • Hepatocyte Growth Factor
  • Proto-Oncogene Proteins c-met