Pathology International · 2001 · 129 citations · 29 references
MedicineMolecular BiologyOncologyMolecular OncologyNeoplasiaSignal TransductionCancer Cell SignalingCancer Molecular PathologyImmunohistochemistryTumor DifferentiationTumor HistopathologyTumor-stroma InteractionsBreast Cancer HistologyBreast Cancer HistopathologyHepatocyte Growth Factor Receptor SignalingHepatocyte Growth Factor SignalingHistologic GradeKi-67 Labeling IndexMalignant Breast TumorsMarker Expression Patterns
Expression of hepatocyte growth factor (HGF) and c-Met (HGF receptor) has been reported in many neoplasms. We investigated coexpression of HGF and c-Met to determine the role of the HGF/c-Met pathway in breast carcinoma, especially at the cancer front. Eighty-eight cases of carcinoma of the breast were studied by immunohistochemistry and by in situ hybridization for HGF and c-Met expression. The staining pattern was termed "front accentuation pattern" when it was most conspicuous at the cancer front. HGF and c-Met proteins were expressed in cancer and stromal cells, with autocrine and paracrine patterns. The front accentuation pattern of c-Met was observed in cancer cells, but not in stromal cells. The front accentuation pattern was not observed in HGF. Coexpression of HGF and c-Met at the cancer front was correlated with histologic grade, reduced patient survival and a high Ki-67 labeling 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 affects some clinical factors, including patient survival.
29
Molecular cloning and expression of human hepatocyte growth factor
Toshikazu Nakamura, Tsutomu Nishizawa, Mitchio Hagiya et al. · Nature · 1989 · 2.2K citations