On the origin of syn- and metachronous urothelial carcinomas.
OBJECTIVE
To evaluate existing models for the origin of meta- and synchronous urothelial carcinomas in light of the accumulated genetic data.


METHODS
Published studies on the clonal origin and genetic relationships of syn- and metachronous tumors, genetic aberrations in normal and premalignant urothelial lesions, as well as histologic and genetic mapping studies of cystectomized bladder samples are reviewed.


RESULTS
The most common models for the origin of syn- and metachronous tumors are found to conform less well to the accumulated genetic data. A new model is proposed, the field-first-tumor-later model, in which aberrant cells with a stem cell, or stem cell-like, origin spread in the urothelium by cellular displacement, creating fields of premalignant cells. Tumor growth is suggested to be initiated by critical genetic events occurring in individual cells in such fields. Hence, recurring tumors are proposed to originate from a shared field of premalignant cells and not from previous overt tumors.


CONCLUSIONS
The proposed model can better account for the existing genetic and histological data on syn- and metachronous urothelial carcinomas.
Höglund
Mattias
M
Department of Clinical Genetics, Lund University Hospital, Lund SE-221 85, Sweden. mattias.hoglund@med.lu.se
D006801:Humans; D019656:Loss of Heterozygosity; D009378:Neoplasms, Multiple Primary / Q000235:genetics / Q000503:physiopathology*; D016609:Neoplasms, Second Primary / Q000235:genetics / Q000503:physiopathology*; D001749:Urinary Bladder Neoplasms / Q000503:physiopathology; D014571:Urologic Neoplasms / Q000235:genetics / Q000503:physiopathology*; D019459:Urothelium / Q000503:physiopathology