Cytogenetic analysis of multifocal bladder cancer supports a monoclonal origin and intraepithelial spread of tumor cells

Bladder cancer is often characterized by a multifocal growth pattern. This observation has given rise to the hypothesis of "field cancerization," pred icting a polyclonal origin of multiple tumors rising from an area of indepe ndently transformed mucosa cells. On the other hand, genetic studies sugges ted a monoclonal origin. To address these contradictory hypotheses, we perf ormed comparative genomic hybridization (CGH) on 32 tumors originating from six bladder cystectomy specimens. All tumors derived from the same patient showed a set of 7-13 identical chromosomal aberrations and additional indi vidual alterations. Most striking were the findings of 17p losses in all (3 2 of 32) tumors of the six cystectomy specimens and 20p gains in all tumors of four bladders, as well as an unexpected high number of chromosomal chan ges (20.4 alterations per tumor on average). To clarify a possible role of the TP53 tumor suppressor gene on 17p13, we applied immunohistochemistry an d sequence analysis on the tumors and additional 52 mucosa samples. Identic al TP53 mutations and protein overexpression was found in individual tumors only as well as in mucosa samples from continuous areas. Our results not o nly provide further evidence for a monoclonal origin of multifocal bladder cancer but also point at intraepithelial migration of tumor cells carrying specific chromosomal aberrations.