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Increased MDR1 gene transcript levels in high-grade carcinoma of the bladder determined by quantitative PCR-based assay

Lookup NU author(s): Professor Steven Clifford, David Thomas, Professor David Neal, Professor John Lunec

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Abstract

Overexpression of the multidrug resistance (mdr1) gene has been implicated in resistance to a number of the chemotherapeutic agents currently used in the treatment of bladder cancer (doxorubicin, vincristine and epirubicin). We report the development and validation of a quantitative assay for the determination of mdr1 gene transcript levels based on reverse transcription and the polymerase chain reaction (PCR), sensitive to less than 2-fold variations in transcript levels. Using these techniques, mdr1 mRNA levels were investigated in 32 primary untreated transitional cell carcinomas of the bladder. mdr1 mRNA was detected in all samples, with levels varying between individual tumours over a 63-fold range. These variations were not associated with the proliferative status of the tumour. mdr1 mRNA levels were significantly higher in poorly differentiated high-grade (G3) tumours than in well- and moderately differentiated low-grade (G1 and G2) tumours (P = 0.0057). The results suggest that this relationship may extend to mdr1 mRNA levels being an indicator of poor prognosis, as anticipated on the basis of the observed relationship to tumour stage and grade. No evidence was found to implicate mdr1 mRNA levels as a predictor of tumour recurrence or progression. Given that mdr1 mRNA levels are increased in a proportion of high-grade bladder tumours that are routinely subjected to chemotherapy, we discuss the possibility that mdr1 mRNA levels may be clinically significant as determinants of chemotherapeutic response and outcome in bladder cancer.


Publication metadata

Author(s): Clifford SC, Thomas DJ, Neal DE, Lunec J

Publication type: Article

Publication status: Published

Journal: British Journal of Cancer

Year: 1994

Volume: 69

Issue: 4

Pages: 680-686

Print publication date: 01/04/1994

ISSN (print): 0007-0920

ISSN (electronic): 1532-1827


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