229 DETECTION OF PROSTATE CANCER METASTASIS USING IN SITU HYBRIDIZATION FOR MEMBRANE-TYPE-1 MATRIX METALLOPROTEASE

Currently prostate cancer is the most commonly diagnosed visceral neoplasm in the male population and the second largest cancer killer of men in the US. While the detection rate of prostate cancer has greatly increased using serum PSA as a screening test, Gleason sum scores and pathologic staging are useful prognostic indicators but cannot accurately predict at the time of biopsy those tumors that will behave aggressively and prove fatal through metastatic dissemination versus those that will remain organ-confined for many years. An important step in metastatic progression of cancer is the remodeling of the extracellular matrix (ECM). Matrix metalloproteases are a family of zinc-dependent enzymes that degrade the components of the ECM in tumor invasion thereby creating a path for migration of neoplastic cells through the basal lamina and into the surrounding stroma. The membrane-type-1 matrix metalloproteases (MT1-MMP), a member of the transmembrane metalloproteases, is found to possess proteolytic activity for ECM proteins including gelatin, fibronectin, K-elastin, vitronectin, collagens and laminin-5 and has been demonstrated to be upregulated in the progression of prostate cancer. In situ hybridization (ISH) techniques have been applied increasingly to localize gene expression at the cytological level. Using reverse-transcriptase polymerase chain reaction (RT-PCR), TOPO cloning, and in vitro synthesis of a unique sequence of MT1-MMP, our aim is to detect its localized expression within prostate cancer sections. Future plans including detecting cadherin and laminin expression patterns on prostate tissue sections.