cyclin D 1 表达对cN2 口腔鳞癌患者TPF 诱导化疗的预测性研究*

目的：探讨cyclinD1 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cyclinD1 蛋白的表达情况，分析cyclinD1 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cyclinD1 检测条件，其中cyclinD1 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，cyclinD1 表达水平与患者行TPF 诱导化疗后的疗效无显著相关性，但cN2 患者中cyclinD1 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：cyclinD1 可作为局部晚期口腔鳞癌患者的预后生物标志物，cyclinD1 高表达的cN2 口腔鳞癌患者可从TPF 诱导化疗中获益。

Cyclin D 1 as a potential predictive biomarker for TPF induction chemotherapy in cN 2 patients with oral squamous cell carcinoma

Objective:To investigate the potential prognostic value of cyclin D 1 expression in patients with locally advanced oral squamous cell carcinoma (OSCC) and its relationship with taxol (Docetaxel)/cisplatin plus 5-fluorouracil (TPF) induction chemothera -py.Methods:A total of 256 patients with locally advanced OSCC were selected from Shanghai Ninth People's Hospital of Shanghai Ji -ao Tong University School of Medicine between March 2008and December 2010as the objects of study in this prospective randomized clinical trial. The effect of TPF induction chemotherapy was investigated. Immunohistochemical staining against cyclin D1 was per-formed in the pretreatment biopsy specimen of the patients. The relationship between cyclin D 1 expression and prognostic data of the TPF induction arm and control arm was analyzed. Results: Cyclin D 1 expression was detected in 232 out of the 256 patients. Patients with low cyclin D1 expression showed significantly better overall survival (OS) (P=0.001), disease-free survival (DFS) ( P=0.003), lo -coregional recurrence-free survival (LRFS) (P=0.004), and distant metastasis-free survival (DMFS) ( P=0.001) than those with high cy-clin D 1 expression. No significant differences existed in OS, DFS, LRFS, or DMFS between the patients with TPF induction chemother-apy and the control. Cyclin D 1 expression levels were not predictive of the benefit from TPF induction chemotherapy in the overall pop -ulation. However, patients with nodal stage cN2 and high cyclin D1 expression, who were undergoing TPF chemotherapeutic regimen, showed significantly higher OS (P=0.024) and DMFS ( P=0.024) than cN 2 patients with high cyclin D 1 expression but undergoing stan -dard surgical treatment. Conclusion:Cyclin D 1 can be used as a prognostic biomarker for patients with locally advanced OSCC. Fur -thermore, cN 2 OSCC patients with high cyclin D 1 expression can receive long-term benefit from the addition of TPF induction chemotherapy to standard surgical treatment.