ORLANDO, FL USA (UroToday.com) - Although BCG remains the intravesical therapy of choice, after TURBT, for high-grade non-muscle invasive bladder carcinomas (NMIBC), a recurrence and progression rate of up to 40% occurs after induction treatment. BCG failure likely can be attributed, at least partially, to inherent tumoral characteristics. The research group aims to seek out differences in gene expression profile between tumors that recurred and those free from recurrence after induction BCG.
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In this prospective study evaluating predictive markers for response to BCG, primary bladder tumors were obtained from patients undergoing TURBT. The analysis was restricted to high-grade Ta and T1 lesions. Tumors were arrayed using the Illumina Platform – DASL v3 to profile tumors for mRNA differential expression (after tumor tissues were identified by a dedicated GU pathologist).
The study compared mRNA expression profiles of 12 primary tumors that responded to BCG with no subsequent recurrences to 5 primary tumors that recurred after BCG. Demographic and tumor stage distribution between the two groups were not statistically different. Median time to recurrence after TURBT was 7 months (range: 4-11 months). Median follow-up for all patients was 50 months. Using Ingenuity Pathway Analysis, the study group found a significant increase in expression of genes within specific functional pathways by tumors that developed recurrence after BCG: cell cycle progression (p=9.2e-5), cell death (p=6.8e-4), necrosis (p=4.54e-4), apoptosis (p=7.4e-3), cell proliferation (p=4.9e-3), migration of antigen presenting cells (p=0.044), and immunological diseases (p=0.015). Highly over-expressed genes include chemokine receptors CXCR2 (fold change (FC) 2.969, p=7.75e-6) and CXCR4 (FC 2.337, p=0.022), nuclear receptor NR4A1 (FC 3.776, p=4.4e-4), and transcription factor SOX2 (FC 2.48, p=1.02e-3).
The authors showed, that compared to BCG-responsive tumors, high-grade NMIBCs that recur after BCG treatment have increased expression of genes implicated in bladder cancer growth and survival, invasion, response to therapy, and metastasis.
Presented by Philip Ho, MD at the American Urological Association (AUA) Annual Meeting - May 16 - 21, 2014 - Orlando, Florida USA
Houston, TX USA
Written by Achim Lusch, MD, University of California (Irvine), and medical writer for UroToday.com