Research article

Microsatellite instability as prognostic marker in bladder tumors: a clinical significance

Minal Vaish^1,3 , Anil Mandhani² , RD Mittal² and Balraj Mittal¹

¹  Departments of Genetics, Sanjay Gandhi Post Graduate Institute of Medical sciences, RaiBariely Road, Lucknow- 226014, India

²  Department of Urology and Renal Sciences, Sanjay Gandhi Post Graduate Institute of Medical sciences, RaiBariely Road, Lucknow- 226014, India

³  Malaria lab, International Centre for Genetic Engineering & Biotechnology, Aruna Asaf Ali Marg, New Delhi-110067

author email corresponding author email

BMC Urology 2005, 5:2doi:10.1186/1471-2490-5-2

Published:	12 January 2005

Abstract

Background

Carcinoma of urinary bladder is one of the leading causes of death in India. Successful treatment of bladder cancer depends on the early detection & specific diagnostic approaches. In the present study, microsatellite instability (MSI) has been evaluated as a prognostic marker in patients with superficial urinary bladder cancer in lower urinary tract for determining risk of recurrence.

Methods

A total of 44 patients with bladder tumors diagnosed with Transitional Cell Carcinomas [TCC] from lower urinary tract were selected for the study. Tumors were staged and graded according to AJCC-UICC (1997) classification and patients were followed with cystoscopy as per the protocol. Polymerase chain reaction (PCR) was done to amplify microsatellite sequences at mononucleotide BAT – 26, BAT – 40, TGFβ RII, IGFIIR, hMSH3, BAX and dinucleotide D2S123, D9S283, D9S1851 and D18S58 loci in blood (control) and tumor DNA. PCR products were separated on 8% denaturing polyacrylamide gel and visualized by autoradiography.

Results

MSI was observed in 72.7% of tumors at BAT – 26, BAT – 40, D2S123, D9S283, D9S1851 and D18S58 loci. Good association of MSI was seen with tumor stage and grade. MSI – High (instability at > 30% of loci) was frequently observed in high stage (40.6%) and high grade (59.4%) tumors. Of 24 tumors of Ta-T1 stage with different grades, 11 (9/18 high grade and 2/6 low grade tumors) recurred in the mean duration of 36 months. MSI positivity was significantly high in patients who had one or more recurrences (p = 0.02 for high grade and 0.04 for low grade tumors).

Conclusions

MSI may be an independent prognostic marker for assessing risk of recurrence in superficial tumors irrespective of the grade. Further studies on progression would help in stratifying the patients of T1G3 for early cystectomy vs bladder preservation protocol.