Coexpression of Keratinocyte Growth Factor and Its Receptor in Normal and Prostate Cancer Tissues: Possible Formation of Autonomous Andromedin Loop

Keratinocyte growth factor (KGF), an androgen-dependent epithelial mitogen, and its receptor (KGFR) have been implicated in the regulation of cell growth and differentiation in prostate tissue. This study was designed to determine the expression and role of KGF and KGFR in normal and prostate cancer tissues, especially in relation to cell kinetics. In 41 cases of prostate cancer in paraffin-embedded specimens, the expression of KGF and KGFR at the levels of protein and mRNA was analyzed by immunohistochemistry using newly raised antibodies and in situ hybridization, respectively. We also examined expression of androgen receptor (AR) and Ki-67 labeling index (LI). In normal and hyperplastic prostate tissues, both KGF mRNA and protein were localized in AR positive stromal cells, while those of KGFR were localized in glandular epithelial cells. In prostate cancer, however, coexpression of KGF and KGFR was observed in 14/41 cases, and significantly correlated with high Gleason scores, bone metastasis and high Ki-67 LI. The relapse-free survival of patients suffering from prostate cancers coexpressing KGF and KGFR was significantly shorter than that of patients from the other ones. Therefore, our results indicate that coexpression of KGF and KGFR in prostate cancer may predict metastatic and proliferative activities, possibly due to the formation of an autonomous andromedin loop.