IMMUNOHISTOCHEMICAL DETECTION OF THE RECEPTOR FOR UROKINASE PLASMINOGEN-ACTIVATOR IN HUMAN COLON-CANCER

Paraffin-wax embedded specimens from 30 cases of colonic adenocarcinom a were investigated for immunoreactivity for the receptor of urokinase -type plasminogen activator (uPAR). In all cases there was a strong si gnal, predominantly at the invasive foci. The positive cells were main ly tumour-infiltrating macrophages but neutrophils and eosinophils wer e also strongly stained. The neoplastic cells were positive in 19 of t he samples with staining of occasional or a moderate number of cells. In uninvolved, normal-appearing mucosa adjacent to the malignant infil trates, immunostaining of both macrophages and neutrophils was seen, b ut the labelling was less intense than that seen in the malignant lesi ons. Weak to moderate staining of normal intestinal epithelium was als o seen at the luminal surface. Comparison between immunoreactivity and in situ hybridization showed a similar distribution of protein and mR NA with two exceptions: first, neutrophils (strongly immunoreactive fo r uPAR) were negative or only weakly positive for uPAR mRNA; and secon d, many cancer cells at invasive foci showed prominent hybridization s ignals but no detectable uPAR immunoreactivity. Together with previous findings of urokinase plasminogen activator (uPA) protein and mRNA be ing expressed in tumour-infiltrating fibroblast-like cells at the inva sive foci, these results support the view that the uPA pathway of plas minogen activation is involved in tissue degradation in colon cancer. The results also extend and consolidate an emerging picture of non-neo plastic tumour stromal cells producing molecules involved in the gener ation and regulation of extracellular proteolysis in cancer.