MMP-3 mRNA and MMP-3 and MMP-1 proteins in bladder cancer: A comparison with clinicopathologic features and survival

Matrix metalloproteinases (MMPs) are proteolytic enzymes important at sever al points during multistep neoplastic progression. Although MMP-1 and MMP-3 have been implicated in the progression of various human cancers, their ex pression in bladder cancer has not been addressed. Immunohistochemistry (St rept-ABC-HRP method) and in situ hybridization were performed to detect MMP -1 protein, MMP-3 protein, and MMP-3 mRNA, respectively, in 59 transitional cell bladder carcinomas. To assess the role of these MMPs in bladder cance r, their expression was evaluated in relation to known clinicopathologic pa rameters and patients' disease-free and overall survival. Immunoreactivity for MMP-1 and MMP-3 proteins was observed in the cytoplasm of cancer cells in 30.5% and 24% of samples, respectively. Transcripts for MMP-3 mRNA were localized in stromal cells in 71.2% of cases and in cancer cells in 49% of cases. MMP-1 immunoreactivity demonstrated a statistically significant asso ciation with deeply invasive and grade III tumors versus superficial and lo wer grade tumors. MMP-3 protein immunoreactivity and MMP-3 mRNA immunolocal ization did not associate with the parameters studied. However, MMP-3 mRNA localization in stromal cells demonstrated a borderline association with po or patients' disease-free and overall survival. In conclusion, the authors' results demonstrate a differential expression between MMP-1 and MMP-3 in b ladder cancer; MMP-1 appears to participate in invasiveness and possibly in loss of differentiation in urothelial carcinomas in contrast to MMP-3.