High levels of hepatocyte growth factor/scatter factor in diffuse-type bronchioloalveolar cell carcinoma.

Abstract

Hepatocyte growth factor/scatter factor (HGF/SF) is a potent mitogen for various neoplastic cells, including neoplastic bronchial epithelia. Immunoreactive hepatocyte growth factor/scatter factor (HGF/SF) was measured in extracts prepared from 129 nonsmall cell lung carcinoma (NSCLC) specimens, using an enzyme-linked immunosorbent assay. These specimens represented 5 cases of solitary/localized bronchioloalveolar cell carcinoma (BAC), 4 cases of diffuse/infiltrative BAC, 90 cases of non-BAC adenocarcinoma, 25 cases of squamous cell carcinoma, and 5 cases of large cell carcinoma. The mean concentration of immunoreactive HGF/SF was more than 19-fold higher in tissue extracts from diffuse-type BAG (265.0 +/- 110.2 ng/100 mg protein) than in those from solitary-type BAC (13.9 +/- 15.9, P < 0.005), non-BAC adenocarcinoma (13.8 +/- 14.9, P < 0.001), squamous cell carcinoma (13.2 +/- 14.4, P < 0.001), or large cell carcinoma (11.2 +/- 6.5, P < 0.005). When immunohistochemical staining for HGF/SF was performed, intense HGF/SF staining was uniformly observed in diffuse-type BAC tumor cells, but not in solitary-type BAC. Although BAC is included as a subtype of adenocarcinoma in the World Health Organization classification, diffuse-type BAC should be considered a distinct biologic entity, at least in terms of HGF/SF expression, from solitary-type BAC or non-BAC adenocarcinoma. In addition, the solitary and diffuse forms of BAC are known to be associated with different prognoses; for the latter, the prognosis is much poorer than for the former. The results of this study may at least partly explain this difference in prognosis.