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目的:探讨cyclin D1在局部晚期口腔鳞癌患者中预后价值以及能否作为多西他赛联合顺铂、5-氟尿嘧啶(TPF)诱导化疗的预测生物标志物。方法:2008年3月至2010年12月上海交通大学医学院附属第九人民医院局部晚期口腔鳞状细胞癌患者256例行TPF诱导化疗的前瞻性随机临床试验为研究对象。随机分为试验组(术前TPF诱导化疗+手术+术后放疗)和对照组(手术+术后放疗)。采用免疫组织化学法检测患者活检标本中cyclin D1蛋白的表达情况,分析cyclin D1表达与行TPF诱导化疗患者预后的关系。结果:256例患者中232例符合cyclin D1检测条件,其中cyclin D1低表达者比高表达者有较高的总生存率(P=0.001)、无病生存率(P=0.003)、无局部复发生存率(P=0.004)和无远处转移生存率(P=0.001)。试验组和对照组之间的患者预后无差异,cyclin D1表达水平与患者行TPF诱导化疗后的疗效无显著相关性,但c N2患者中cyclin D1高表达者可从TPF诱导化疗在总生存率(P=0.024)和无远处转移生存率(P=0.024)中获益。结论:cyclin D1可作为局部晚期口腔鳞癌患者的预后生物标志物,cyclin D1高表达的c N2口腔鳞癌患者可从TPF诱导化疗中获益。
Objective: To investigate the prognostic value of cyclin D1 in patients with locally advanced oral squamous cell carcinoma and its potential as a predictive biomarker for docetaxel plus cisplatin and 5-fluorouracil (TPF) -induced chemotherapy. Methods: From March 2008 to December 2010, 256 patients with locally advanced oral squamous cell carcinoma of the Ninth People’s Hospital Affiliated to Shanghai Jiaotong University School of Medicine underwent prospective randomized clinical trials of TPF induction chemotherapy. Randomly divided into experimental group (preoperative TPF induction chemotherapy + surgery + postoperative radiotherapy) and control group (surgery + postoperative radiotherapy). The expression of cyclin D1 in biopsy specimens was detected by immunohistochemistry. The relationship between cyclin D1 expression and the prognosis of patients undergoing TPF induction chemotherapy was analyzed. Results: Of the 256 patients, 232 patients were eligible for cyclin D1 test. The patients with low expression of cyclin D1 had higher overall survival (P = 0.001), no disease-free survival (P = 0.003) and no local recurrence Survival rates (P = 0.004) and distant metastasis-free survival (P = 0.001). There was no difference in prognosis between the experimental group and the control group. There was no significant correlation between the expression of cyclin D1 and the curative effect after TPF induction chemotherapy in patients. However, the high expression of cyclin D1 in c N2 patients could be observed in the overall survival rate (P = 0.024) and distant metastasis-free survival (P = 0.024). Conclusions: Cyclin D1 can be used as a prognostic biomarker in patients with locally advanced oral squamous cell carcinoma. Patients with cyclin D1-overexpressing c N2 oral squamous cell carcinoma may benefit from TPF-induced chemotherapy.