CELLULAR-LOCALIZATION BY IN-SITU HYBRIDIZATION OF CATHEPSIN-D, STROMELYSIN-3, AND UROKINASE PLASMINOGEN-ACTIVATOR RNAS IN BREAST-CANCER

We have compared by RNA in situ hybridisation on serial cryo-sections the distribution of cathepsin D (cath-D), stromelysin 3 (strom-3), and urokinase plasminogen activator (UPA) gene expression in different ti ssues of human benign and malignant mammary tumors. Cath-D expression was found to be higher in adenocarcinomas compared to non-tumoral glan ds. The cath-D RNA was located in mammary epithelial cancer cells rath er than in fibroblasts, indicating that the cath-D gene was overexpres sed in cancer cells, where the corresponding protein determined by imm unohistochemical staining had been shown to be accumulated (P. Roger e t al., Human Pathol 25: 863-871, 1994). In contrast strom-3 RNA in adj acent tissue sections used as a control of tissue localisation was mos tly expressed in peritumoral fibroblasts rather than in cancer cells c onfirming previous results of Basset et al. and validating our methodo logy. UPA RNA was detected both in tumor cells and in stromal cells. T n benign lesions the 3 protease RNAs were mostly found in epithelial c ells. Stromal cells expressed UPA. RNA in 5 of 7 lesions, cath-D and s trom-3 in only one sample. We conclude that in breast cancer patients, cath-D gene expression is increased in epithelial mammary cancer cell s at the RNA level as well as at the protein level? suggesting an alte red transcriptional regulation. In non malignant lesions, the distribu tion was different with a predominant distribution in epithelial mamma ry cells for the 3 protease messenger RNA.