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

Expression of hepatocyte growth factor (HGF) and c-Met (HGF receptor) has b een reported in many neoplasms. We investigated coexpression of HGF and c-M et to determine the role of the HGF/c-Met pathway in breast carcinoma, espe cially at the cancer front. Eighty-eight cases of carcinoma of the breast w ere studied by immunohistochemistry and by in situ hybridization for HGF an d c-Met expression. The staining pattern was termed 'front accentuation pat tern' when it was most conspicuous at the cancer front. HGF and c-Met prote ins were expressed in cancer and stromal cells, with autocrine and paracrin e patterns. The front accentuation pattern of c-Met was observed in cancer cells, but not in stromal cells. The front accentuation pattern was not obs erved in HGF. Coexpression of HGF and c-Met at the cancer front was correla ted with histologic grade, reduced patient survival and a high Ki-67 labeli ng 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 affec ts some clinical factors, including patient survival.