Open Access

ARTICLE

Microsatellite instability in multifocal urothelial carcinoma and effect on BAX and AXIN2

Annette M. Walsh¹, Gregory G. Bailly², David G. Bell², Richard W. Norman², Rekha Gupta¹, Ekram Zayed¹, Bassam A. Nassar^1,3,*

1 Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada
2 Department of Urology, Dalhousie University, Halifax, Nova Scotia, Canada
3 Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
Address correspondence to Dr. Bassam A. Nassar, Division of Clinical Chemistry, Queen Elizabeth II Health Sciences Centre, 1278 Tower Road, Halifax, N.S., B3H 2Y9, Canada

Canadian Journal of Urology 2003, 10(5), 2000-2006.

Abstract

Objectives: Urothelial carcinomas have a synchronous or metachronous multifocal pattern of occurrence, questioning their clonal origin. Genetic alterations such as microsatellite instability (MSI) affect various tumors including urothelial cancers. These alterations can affect repeat sequences and cause mutations in coding regions of genes involved in transformation, tumor suppression and apoptosis. Recently, the eight-guanine (G₈) and the seven-guanine (G₇) repeat sequences of the BAX and AXIN2 genes respectively, were shown altered in different cancers. Since BAX is involved in apoptosis while the AXIN2 is involved in β-catenin metabolism, a protein involved in cell adhesion and DNA transcription, and due to the multifocal nature of urothelial cancer, we investigated these two genes for alterations in repeat sequences in patients with this cancer.
Patients and methods: The eight microsatellites BAT25, BAT26, D2S123, D3S1029, D5S346, D17S588, D17S261, MYCL1 were used to screen 25 tumors from seven patients with eight upper and 17 lower urinary tract carcinomas and compare them to DNA from normal tissue. Regions spanning the G₈ and G₇ repeat sequences of BAX and AXIN2 were sequenced for mutations including expansion and deletion abnormalities.
Results: Six microsatellites were seen altered in one patient with kidney and bladder cancer affecting both tissues when compared to normal DNA albeit not similarly except for MYCL1. There was no change in the BAX G₈ or AXIN2 G₇ microsatellites. There was no MSI seen in any of the remaining six patients.
Conclusion: MSI occurs in urothelial cancer, but was not seen to affect the BAX G₈ or AXIN2 G₇ repeats in this study. However, to determine if MSI affects these genes in these tumors will require a larger study. Moreover, our results suggest that these tumors may have a monoclonal origin with further genetic changes resulting in oligoclonality, or could suggest a similar initiating event leading to a similar initial genetic alteration at different sites with subsequent varying events due to a genetically unstable malignant phenotype.

---

Keywords

---