Superficial and metachronous invasive bladder carcinomas are clonally related

Synchronous and metachronous tumors are frequently observed in the urinary tract and may be explained by the concept of 'fieldcancerization,' i.e., ex posure to carcinogens leading to the independent transformation of many uro thelial cells resulting in oncogenetically unrelated tumors. Increasing evi dence, however, supports the concept of clonality, i.e., the progeny of a s ingle transformed cell spreads through the urinary system resulting in gene tically related tumors. The aim of our study was to investigate the putativ e clonal origin of invasive urothelial cell carcinomas (UCCs) of the bladde r from a prior superficial tumor. We selected 6 patients (5 males and 1 fem ale) with superficial and subsequent invasive UCC tumors. All patients were previously diagnosed with a p53 mutation in their invasive tumor. At least 1 superficial and 1 invasive tumor of the same patient were analyzed for m utations in the p53 tumor suppressor gene by PCR-SSCP and, in case of a ban d shift, followed by direct sequencing. In all patients the same p53 mutati on was found in the superficial and subsequent invasive tumor(s). All tumor s arose from the same progenitor cell. These results support the concept of a clonal origin of superficial and metachronous invasive bladder UCCs. (C) 2001 Wiley-Liss, Inc.