Scatter factor protein levels in human breast cancers: clinicopathological and biological correlations

Scatter factor (SF) is an invasogenic and angiogenic cytokine the cellular receptor of which is encoded by a proto-oncogene (c-met). We measured the immunoreactive SF content (nanograms of SF per milligram of protein) in tissue extracts from 166 breast cancers and correlated the values with various known prognostic parameters. Invasive cancers had nearly four times greater SF content than did ductal carcinoma in situ, and the difference was statistically significant (P < 0.02, two-tailed t-test). However, there were no significant differences in SF content among different histological types of invasive cancer. Invasive cancers that had spread to axillary lymph nodes exhibited higher SF content than did invasive cancers without regional spread (P < 0.02), but the difference in SF content between node-positive and node-negative tumors was not as great as that between invasive and ductal carcinoma in situ tumors. There was a trend toward increased SF content in larger primary tumors as compared with smaller tumors, but statistical comparison revealed borderline significance (0.05 < P < 1.0). There was no significant correlation between SF content and other parameters, including estrogen receptor, progesterone receptor, DNA ploidy, S phase, or Scarff-Bloom-Richardson score. We also measured the content of von Willebrand factor (a marker of blood vessels) and interleukin-1 beta (a pro-inflammatory cytokine) in the same tumor extracts. SF content showed a strong positive correlation with von Willebrand factor content (P < 0.001) but did not appear to be correlated with interleukin-1 beta. These findings suggest that SF is correlated with several other clinicopathological indicators of aggressive tumor behavior, consistent with the hypothesis that SF is a biological factor that may play a role in breast cancer pathogenesis.