Recurrent and multiple bladder tumors show conserved expression profiles

David Lindgren¹ , Sigurdur Gudjonsson² , Kowan Ja Jee³ , Fredrik Liedberg² , Sonja Aits¹ , Anna Andersson¹ , Gunilla Chebil⁴ , Åke Borg⁵ , Sakari Knuutila³ , Thoas Fioretos¹ , Wiking Månsson² and Mattias Höglund¹

¹Department of Clinical Genetics, Lund University Hospital, Lund, Sweden

²Department of Urology, Lund University Hospital, Lund, Sweden

³Department of Pathology, Haartman Institute and HUSLAB, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland

⁴Department of Pathology and Cytology, Helsingborg Hospital, Helsingborg, Sweden

⁵Department of Oncology, Lund University Hospital, Lund, Sweden

author email corresponding author email

BMC Cancer 2008, 8:183doi:10.1186/1471-2407-8-183


Published:	30 June 2008

Abstract

Background

Urothelial carcinomas originate from the epithelial cells of the inner lining of the bladder and may appear as single or as multiple synchronous tumors. Patients with urothelial carcinomas frequently show recurrences after treatment making follow-up necessary. The leading hypothesis explaining the origin of meta- and synchronous tumors assumes a monoclonal origin. However, the genetic relationship among consecutive tumors has been shown to be complex in as much as the genetic evolution does not adhere to the chronological appearance of the metachronous tumors. Consequently, genetically less evolved tumors may appear chronologically later than genetically related but more evolved tumors.

Methods

Forty-nine meta- or synchronous urothelial tumors from 22 patients were analyzed using expression profiling, conventional CGH, LOH, and mutation analyses.

Results

We show by CGH that partial chromosomal losses in the initial tumors may not be present in the recurring tumors, by LOH that different haplotypes may be lost and that detected regions of LOH may be smaller in recurring tumors, and that mutations present in the initial tumor may not be present in the recurring ones. In contrast we show that despite apparent genomic differences, the recurrent and multiple bladder tumors from the same patients display remarkably similar expression profiles.

Conclusion

Our findings show that even though the vast majority of the analyzed meta- and synchronous tumors from the same patients are not likely to have originated directly from the preceding tumor they still show remarkably similar expressions profiles. The presented data suggests that an expression profile is established early in tumor development and that this profile is stable and maintained in recurring tumors.