Stromelysin-3 expression in noninvasive and invasive neoplasms of the urinary bladder

Stromelysin-3 (ST-3) is a protease frequently expressed by fibroblasts surrounding invasive carcinomas. Based on its expression in some cases of breast carcinoma-in-situ, it has been thought to indicate a higher likelihood for subsequent invasion in preinvasive lesions. Carcinoma-in-situ (pTis) and noninvasive papillary tumor (pTa) of the urinary bladder are preinvasive lesions with an uncertain potential to become invasive. We studied the expression of ST-3 in pTis, pTa, and invasive bladder tumors to see whether it had an association with any established histopathologic variables and whether its expression might be an indicator of incipient invasion in the preinvasive lesions. Twenty-seven pTis, 27 pTa tumors, and 56 invasive bladder carcinomas were studied for ST-3 expression with immunohistochemistry and, in selected cases, with in situ hybridization. Staining for ST-3 was evaluated semiquantitatively. None of 27 pTis lesions, 4 of 27 pTa tumors, and 41 of 56 (73.2%) invasive carcinomas were positive for ST-3. Statistically significant associations were found in the invasive carcinomas between ST-3 expression and lymphatic vessel invasion, an infiltrative invasive pattern, and invasion into at least the muscle layer (pT2,3,4 v pT1). The expression of ST-3 in frankly invasive tumors was associated with a more aggressive tumor phenotype. Its expression in a small subgroup of pTa lesions may be indirect evidence that some tumors diagnosed as pTa have invasive potential.