COEXPRESSION OF HEPATOCYTE GROWTH-FACTOR AND RECEPTOR (MET) IN HUMAN BREAST-CARCINOMA

Expression of hepatocyte growth factor (HGF) and HGF receptor (HGFR, p roduct of the met proto-oncogene) mRNA were examined by nonisotopic in situ hybridization in a spectrum of benign and malignant human breast tissues, mRNA for both HGFR and HGF was detected in benign ductal epi thelium. Epithelial expression of HGF mRNA was particularly intense in regions of ductal epithelial hyperplasia. Positive expression of HGF (but not HGFR) mRNA was also found in adipocytes, endothelial cells, a nd to varying degrees in stromal fibroblasts. In 12 of 12 cases of duc tal carcinoma in situ and infiltrating ductal carcinoma, carcinoma cel ls showed a heterogeneous pattern of expression for both HGFR and HGF mRNA. In infiltrating ductal carcinomas, intense expression of HGFR mR NA was not restricted to ductular structures but was also seen in non- duct-forming carcinoma cells. The same zones of the tumors (most commo nly at the advancing margins) that expressed strongly HGFR mRNA often were also strongly positive for HGF mRNA, suggesting a possible autocr ine effect, The expression pattern of HGFR protein in 25 cases includi ng the same series of tissues used for in situ hybridization analysis was similar to that of HGFR mRNA, as determined by an immunoperoxidase technique. The finding that HGFR is expressed by both benign and mali gnant epithelium, and is not restricted to duct-forming structures, su ggests that, although the potential for HGF/HGFR binding is maintained in malignancy, the response to ligand binding at the level of the rec eptor or the cellular response to receptor activation may change at so me point during progression.