Japanese Journal of Clinical Oncology 34:124-130 (2004)
© 2004 Foundation for Promotion of Cancer Research
Bax to Bcl-2 Ratio and Ki-67 Index are Useful Predictors of Neoadjuvant Chemoradiation Therapy in Bladder Cancer
Department of Urology, Yamaguchi University School of Medicine, Ube, Japan
Objective: In this study, locally advanced bladder cancer was treated by radiation combined with cisplatin therapy and a retrospective analysis was conducted to predict the clinical response to chemoradiotherapy (CRT) based on the immunohistochemistry of apoptosis-related proteins.
Methods: Sixty-two patients (median age, 68 years; range, 45–89 years) with transitional cell carcinoma of the bladder (pT1G3–pT4M0) treated with CRT (median dose: 40.5 Gy of radiation and 230 mg of cisplatin) were studied. Mucosal biopsy was performed before and after CRT. Paraffin-embedded tumor specimens were examined with TUNEL and were immunostained for Ki-67, p53, Bcl-2 and Bax; the Bax/Bcl-2 ratio and apoptosis index (AI) were calculated. Clinical features of the patients and response to CRT were compared with data obtained from examination of the tumors.
Results: The 62 patients had a median follow-up period of 34 months (range, 3–84 months). Responses to CRT were as follows: CR, 34%; PR, 45%; NC, 21%. The survival rate of patients with Ki-67-positive tumors was significantly lower than those of patients with Ki-67-negative tumors (P < 0.05). No significant correlation was observed between the expression of any protein, the AI and the clinical response. However, the Bax/Bcl-2 ratio showed a significant association with the CR rate (P = 0.0289).
Conclusions: The results of this study suggest that the combined assessment of Bcl-2 and Bax protein expression may be used to predict a clinical response to CRT based on the Bax/Bcl-2 ratio determined before therapy. The Ki-67 index may be a useful predictor of prognosis in patients treated by CRT.
+ For reprints and all correspondence: Katsusuke Naito, Department of Urology, Yamaguchi University School of Medicine, 1–1-1, Minami-Kogushi, Ube, Yamaguchi 755–8505, Japan. E-mail: katsunai{at}po.cc.yamaguchi-u.ac.jp
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