Prognostic significance of co-expression of RON and MET receptors in node-negative breast cancer patients.

Abstract

PURPOSE:

RON and MET belong to a subfamily of tyrosine kinase receptors. They both can induce invasive growth, including migration, cell dissociation, and matrix invasion. Cross-linking experiments show that RON and MET form a noncovalent complex on the cell surface and cooperate in intracellular signaling. We wanted to examine the clinical significance of RON and MET expression patterns in node-negative breast cancer.

EXPERIMENTAL DESIGN:

We studied the protein expressions of RON and MET in five breast cancer cell lines and a homogeneous cohort of 103 T(1-2)N(0)M(0) breast carcinoma patients, including 52 patients with distant metastases and 51 patients with no evidence of disease after at least a 10-year follow-up.

RESULTS:

Both HCC1937 and MDA-MB-231 cancer cell lines co-overexpressed RON and MET. The MCF-7 cell line did not express RON or MET. In multiple logistic regression analysis, RON expression (odds ratio, 2.6; P = 0.05) and MET expression (odds ratio, 4.7; P = 0.009) were independent predictors of distant relapse. RON+/MET+ and RON-/MET+ tumors resulted in a large risk increase for 10-year disease-free survival after adjusting for tumor size, histologic grade, estrogen receptor, bcl-2, HER-2/neu, and p53 status by multivariate Cox analysis (risk ratio, 5.3; P = 0.001 and risk ratio, 3.76; P = 0.005). The 10-year disease-free survival was 79.3% in patients with RON-/MET- tumors, was only 11.8% in patients with RON+/MET+ tumors, and was 43.9% and 55.6% in patients with RON-/MET+ and RON+/MET- tumors.

CONCLUSIONS:

Co-expression of RON and MET seems to signify an aggressive phenotype in node-negative breast cancer patients.

• Authors: Wen-Ying Lee, Helen H W Chen, Nan-Haw Chow, Wu-Chou Su, Pin-Wen Lin, How-Ran Guo
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 11 Issue 6 Pg. 2222-8 (Mar 15 2005) ISSN: 1078-0432 [Print] United States
• PMID: 15788670 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Proto-Oncogene Proteins
• Proto-Oncogene Proteins c-bcl-2
• Receptors, Estrogen
• Receptors, Growth Factor
• Tumor Suppressor Protein p53
• Hepatocyte Growth Factor
• MET protein, human
• Proto-Oncogene Proteins c-met
• RON protein
• Receptor Protein-Tyrosine Kinases
• Receptor, ErbB-2

Topics

• Adult
• Aged
• Breast Neoplasms (metabolism, pathology)
• Cohort Studies
• Female
• Hepatocyte Growth Factor (metabolism)
• Humans
• Lymph Nodes (pathology)
• Middle Aged
• Neoplasm Invasiveness (pathology)
• Neoplasms, Ductal, Lobular, and Medullary (metabolism, secondary)
• Prognosis
• Proto-Oncogene Proteins (metabolism)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Proto-Oncogene Proteins c-met
• Receptor Protein-Tyrosine Kinases (metabolism)
• Receptor, ErbB-2 (metabolism)
• Receptors, Estrogen (metabolism)
• Receptors, Growth Factor (metabolism)
• Survival Rate
• Tumor Cells, Cultured
• Tumor Suppressor Protein p53 (metabolism)