EXPRESSION OF SCATTER FACTOR AND C-MET RECEPTOR IN BENIGN AND MALIGNANT BREAST-TISSUE

BACKGROUND, Scatter factor (SF), also known as hepatocyte growth facto r, is an angiogenic cytokine that stimulates epithelial cell motility and invasion. Its receptor is a transmembrane tyrosine kinase encoded by the c-met protooncogene. Several prior experimental and clinical st udies have suggested that SF might play a role in the development and progression of breast carcinoma. To investigate the possible involveme nt of SF and c-met in the evolution of breast carcinoma, the authors s tudied their expression in sections of human breast tissue. METHODS, A variety of paraffin embedded tissue specimens (of normal breast tissu e tissue, benign hyperplasia, ductal carcinoma-in-situ [DCIS], and inv asive ductal carcinoma) from 125 patients were immunoperoxidase-staine d using specific antisera against SF and c-met. The staining intensiti es of epithelial mammary cells were scored semiquantitatively, and the staining scores were analysed as a function of tissue type. In additi on, in situ hybridization to detect SF mRNA was performed for a small number of cancer sections. RESULTS, Specific SF staining was observed in tumor cells, normal cell types (epithelium and vascular smooth musc le), and acellular stroma, whereas c-met staining was observed in tumo r cells and normal cell types but not in stroma. Analysis of the stain ing scores of epithelial mammary cells revealed several patterns: (1) SF and c-met staining scores each increased in the following order: no rmal breast/benign hyperplasias (lowest) --> DCIS (higher) --> invasiv e carcinoma (highest); (2) normal-appearing mammary ducts and lobules in invasive cancer sections showed less SF and c-met staining than tum or cells in the same specimens but more staining than normal ducts and lobules in sections of normal breast tissue and benign hyperplasia; ( 3) within the DCIS and invasive cancer groups, SF and c-mer staining s cores were correlated; and (4) among 40 consecutive cases of DCIS, hig her levels of SF and c-mel staining showed a trend toward association with other features suggestive of aggressive tumor biology (comedo his tology, high nuclear grade, p53 positivity, and bcl-2 negativity). In situ hybridization analysis revealed that the same cell types that exp ressed SF protein (including tumor cells) also expressed SF mRNA trans cripts. CONCLUSIONS, SF and c-met are overexpressed in breast carcinom a as compared with benign breast tissue, and they tend to be coexpress ed in cancerous tissue. These findings are consistent with the idea th at the SF:c-met ligand:receptor pair may have a role in breast carcino ma progression. (C) 1997 American Cancer Society.