Login to Access Video or Poster Abstract: MP88-02
Sources of Funding: The authors declare no conflict of interest associated with this manuscript.

Introduction

Class III beta-tubulin (TUBB3) is associated with malignant aggressiveness and prognosis, in addition, its expression is recognized as a predictive marker for taxane-based chemotherapy (CTx) in several cancers. In urothelial cancer (UC), standard first-line therapy for advanced disease is cisplatin (CDDP)-based CTx. On the other hand, although second-line regimen for CDDP-resistant tumor is not still established, several studies showed paclitaxel (PTX)-based regimens were effective to improve the prognosis. The main aim is to clarify the predictive value of TUBB3 expression for anti-cancer effect by first-line CDDP-based CTx and second-line PTX-based one in patients with UC.

Methods

We reviewed 116 UC (bladder cancer = 90 and upper urinary tract cancer = 26) patients treated with CDDP-based regimen as first-line CTx. Among these patients, 53 patients were received PTX-based second-line CTx. As PTX-based CTx, the combination of gemcitabine and PTX were performed in 42 patients. TUBB3 expression was evaluated by immunohistochemical technique, and survival analyses were performed by using Kaplan-Meier survival curves and multivariate COX proportional hazard analysis.

Results

Positively stained ratio of TUBB3 in grade 3 tumors (50 / 74 = 67.6%) was significantly higher (P < 0.001) than that in grade 1 (0 / 5 = 0.0%) and grade 2 (14 / 37 = 37.8%). A similar trend was found in T stage; however, it did not reach the significant level (P = 0.062). No significant relationship was found in age, sex, and metastasis. When the predictive value of TUBB3 expression for CDDP-based first-line CTx was investigated, it is not recognized as a significant predictive factor for progression-free survival (P = 0.796). On the other hand, high expression of TUBB3 is significantly associated with unfavorable overall survival from starting of second-line CTx (P = 0.013). Multivariate analysis model including all pathological features, part of a tumor, and regimen of second-line therapy showed that TUBB3 expression was identified as an independent predictor (hazard ratio = 5.18, 95% confidential intervals = 1.85 - 14.53, P = 0.002).

Conclusions

The TUBB3 expression is associated with malignant potential in UC. TUBB3 expression was identified as a useful predictive factor for anti-cancer effects of second-line PTX-based CTx in advanced UC patients with CDDP-resistant tumors. Out information is useful to discuss treatment strategies for patients with CDDP-resistant UC.

Funding

The authors declare no conflict of interest associated with this manuscript.