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


METHODS
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.
Lee
Wen-Ying
WY
Department of Pathology, College of Medicine, National Cheng Kung University, Chi Mei Medical Center, 901 Chung Hwa Road, Yung Kang City, Tainan 710, Taiwan. 7707@so-net.net.tw
Chen
Helen H W
HH
Chow
Nan-Haw
NH
Su
Wu-Chou
WC
Lin
Pin-Wen
PW
Guo
How-Ran
HR
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology*; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D018299:Neoplasms, Ductal, Lobular, and Medullary / Q000378:metabolism / Q000556:secondary; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000378:metabolism*; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D017228:Hepatocyte Growth Factor; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D017978:Receptors, Growth Factor; D016159:Tumor Suppressor Protein p53; C491743:MET protein, human; C080835:RON protein