Bax to Bcl-2 Ratio and Ki-67 Index are Useful Predictors of Neoadjuvant Chemoradiation Therapy in Bladder Cancer

• Published in: Japanese journal of clinical oncology Vol. 34; no. 3; pp. 124 - 130
• Main Authors: Matsumoto, Hiroaki, Wada, Takashi, Fukunaga, Koji, Yoshihiro, Satoru, Matsuyama, Hideyasu, Naito, Katsusuke
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.03.2004; Oxford Publishing Limited (England)
• Subjects: Aged; Aged, 80 and over; Antineoplastic Agents - therapeutic use; Apoptosis; bcl-2-Associated X Protein; Bladder cancer; Carcinoma, Transitional Cell - drug therapy; Carcinoma, Transitional Cell - metabolism; Carcinoma, Transitional Cell - mortality; Carcinoma, Transitional Cell - radiotherapy; Cisplatin - therapeutic use; Female; Humans; Key words: bladder cancer – chemoradiotherapy – apoptosis – immunohistochemistry – Bax/Bcl-2 ratio; Ki-67 Antigen - biosynthesis; Male; Middle Aged; Neoadjuvant Therapy; Prognosis; Proto-Oncogene Proteins - biosynthesis; Proto-Oncogene Proteins c-bcl-2 - biosynthesis; Radiotherapy Dosage; Retrospective Studies; Survival Rate; Tumor Suppressor Protein p53 - biosynthesis; Urinary Bladder Neoplasms - drug therapy; Urinary Bladder Neoplasms - metabolism; Urinary Bladder Neoplasms - mortality; Urinary Bladder Neoplasms - radiotherapy
• ISSN: 0368-2811; 1465-3621; 1465-3621
• DOI: 10.1093/jjco/hyh026

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.