Postchemotherapy AKR1B10 expression correlates with disease-free survival in muscle-invasive bladder cancer.

Abstract

319 Background: AKR1B10 is a member of the aldo-keto reductase superfamily of NAD(P)H-dependent oxidoreductases.AKR1B10 is considered to contribute to cell proliferation and chemo-resistance. In the present study, we examined whether AKR1B10 expression correlates with disease free survival in bladder cancer specimens. Methods: The cohort includes consecutive 57 patients with muscle-invasive bladder cancer who received neoadjuvant chemotherapy followed by radical cystectomy. All patients received two cycles of neoadjuvant chemotherapy with gemcitabine plus carboplatin. Bladder cancer specimens were obtained at pre- and post-neoadjuvant chemotherapy, which were subjected to quantitative real-time PCR and immunohistochemistry to evaluate AKR1B10 expression. Intensity scoring for immunohistochemistry was categorized using a 4-graded scoring system according to a previously published method, with positive cells for each specific marker expressed as a percentage of the total number of cells as follows: 0%–10% = 0; 11%–30% = 1; 31%–70% = 2; 71%–100% = 3. Results: AKR1B10 mRNA expression was significantly higher in the post-chemotherapy groups than in the pre-chemotherapy groups (p < 0.001). The average immunohistochemical intensity score in the pre-chemotherapy group was 0.83 ± 1.08, compared to a significantly higher average intensity score of 2.03 ± 1.03 in the post-chemotherapy group (p < 0.001) Disease free survival of the post-chemotherapy AKR1B10(+) patients (61.2%) was significantly lower than that of AKR1B10(−) patients (100%) (log-rank test: p = 0.039). Conclusions: Although the present study is small and preliminary, post-chemotherapy AKR1B10 expression may have a predictive potential for response of chemotherapy and disease recurrence after definitive therapy for muscle-invasive bladder cancer. Further study is warranted to elucidate its clinical significance.