Expression of keratinocyte growth factor/fibroblast growth factor-7 and its receptor in human lung cancer: correlation with tumour proliferative activity and patient prognosis

Keratinocyte growth factor (KGF)/fibroblast growth factor-7 (FGF-7), a mesenchymal cell-derived paracrine growth factor that specifically stimulates epithelial cell proliferation, has been implicated in the repair of lung tissue. The present study was designed to determine the expression and role of KGF and its receptor (KGFR) in human lung cancer tissues, particularly in relation to cancer cell kinetics and prognosis. Thirty-one adenocarcinomas and 30 squamous cell carcinomas, and ten normal lung tissues as a control, were examined. The expression of KGF and KGFR proteins was examined using rabbit polyclonal antihuman KGF and anti-human KGFR antisera raised in the authors' laboratories against synthetic peptides corresponding to parts of human KGF and KGFR, respectively. Their specificity was confirmed in lung tumour tissues by western blotting and various controls. Proliferative activity was assessed by determining the labelling index (LI) for Ki-67 antigen. Immunohistochemistry revealed that tissue co-expression of KGF and KGFR correlated significantly with higher differentiation grades in squamous cell carcinoma. Conversely, in adenocarcinoma, co-expression correlated with lower differentiation grades and high Ki-67 LI, and was significantly associated with lymph node metastasis and shorter 5-year survival. Therefore, the results indicate that co-expression of KGF and KGFR correlates significantly with poor prognosis in adenocarcinoma, but not in squamous cell carcinoma, of the lung. Copyright (C) 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley Sons, Ltd.