Localization of messenger RNA for matrix metalloproteinase-2 and -9, and tissue inhibitor of metalloproteinase-2 in human benign and malignant prostatic tissue by in situ hybridization

Introduction: Metastasis is a multistage process involving degradation of the extracellular matrix. The matrix metallo-proteinases (MMPs) are thought to play a role in the tissue degradation that occurs when a tumour cell metastasises. The activity of MMPs is regulated by the tissue inhibitor of the metalloproleinase (TIMP) family. The aim of this study was to identify the phenotype of cells expressing mRNA for MMP-2. MMP-9 and TIMP-2 in benign and malignant prostatic tissue using non-isotopic in situ hybridization. Patients and methods: Twenty men were investigated; 13 had newly diagnosed, untreated prostate cancer and seven had BPH. Specific riboprobes were transcribed using the digoxigenin transcription method. Results: MMP-2 and TIMP-2 were expressed by malignant cells in low- and high-grade tumours. In the former, the signal was localized at the luminal edge. TIMP-2 and MMP-2 were also expressed within areas of perineural and extracapsular invasion. Positive signals for both genes were detected in epithelial cells of benign glands and ejaculatory ducts. Areas of PIN were negative with both probes. MMP-9 was expressed in five of seven cases with metastatic disease in malignant epithelial cells and areas of PIN were positive in three of 20 cases. Staining in BPH tissue was predominantly basal but a strong signal was observed at the luminal edge of many glands. Adjacent benign tissue and stromal tissue were negative with all probes. Conclusions: These results show the presence of mRNA for MMP-2 and -9 and their inhibitor TIMP-2 in epithelial cells of both benign and malignant prostatic tissue. The patterns of expression appear to differ in the presence of carcinoma. In particular, the detection of MMP-2 and TIMP-2 within areas of tumour invasion suggests that these enzymes may play a significant role in the process of invasion in prostate cancer, offering potential for future therapeutic manipulation.