Bax to Bcl-2 ratio and Ki-67 index are useful predictors of neoadjuvant chemoradiation therapy in bladder cancer

Bax to Bcl-2 ratio and Ki-67 index are useful predictors of neoadjuvant chemoradiation therapy in bladder cancer
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DOI:
10.1093/jjco/hyh026
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发表时间:
2004-03-01
影响因子:
2.4
通讯作者:
Naito, K
Naito, K
中科院分区:
医学4区
文献类型:
--
作者:
Matsumoto, H;Wada, T;Naito, K

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目的:采用放射治疗联合顺铂治疗局部晚期膀胱癌,并基于细胞凋亡相关蛋白的免疫组织化学方法,对放化疗的临床疗效进行回顾性分析。方法:62例膀胱移行细胞癌(pT1G3-pT4M0)患者,中位年龄68岁,年龄45-,中位剂量放疗40.5Gy230 mg。分别于CRT前、后行胃黏膜活检。采用原位末端标记法(TUNEL)检测石蜡包埋肿瘤标本中Ki-67、P53、Bcl2和Bax的表达,计算Bax/Bcl2比值和细胞凋亡指数(AI)。结果:62例患者的中位随访时间为34个月(3-84个月)。CRT有效率为34%,PR为45%,NC为21%。Ki-67阳性患者的生存率显著低于Ki-67阴性患者(P<0.05)。未观察到任何蛋白的表达和AL与临床疗效之间的显著相关性。Bax/Bcl2比值与CR率呈正相关(P=0.0289)。结论:根据治疗前测定的Bax/Bcl2比值,联合检测Bcl2和Bax蛋白表达可预测CRT的临床疗效。Ki-67指数可能是预测CRT患者预后的有用指标。
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 Al 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.