Excision repair cross complementation group1 immunohistochemical expression predicts objective response and cancer-specific survival in patients treated by cisplatin-based induction chemotherapy for locally advanced head and neck squamous cell carcinoma
Excision repair cross complementation group1 immunohistochemical expression predicts objective response and cancer-specific survival in patients treated by cisplatin-based induction chemotherapy for locally advanced head and neck squamous cell carcinoma
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DOI：
10.1158/1078-0432.ccr-07-0252
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发表时间：
2007-07-01
影响因子：
11.5
通讯作者：
Fouret, Pierre
中科院分区：
文献类型：
--
作者：
Handra-Luca, Adriana;Hernandez, Juana;Fouret, Pierre
目的：评估接受顺铂诱导化疗的局部晚期头颈部鳞状细胞癌患者中切除修复交叉互补组1（ERCC 1）免疫组化表达与客观肿瘤缓解和癌症特异性生存期的相关性。初始队列由107名患者组成，这些患者于1992年至1996年间接受了局部晚期头颈部鳞状细胞癌诱导化疗方案的治疗。p53基因突变以前曾被研究过。可获得96例已知肿瘤缓解患者的治疗前活检样本。两名对临床注释不知情的独立观察者评估了ERCC 1免疫组化表达。结果：在96名患者中，68例（71%; 95%置信区间，61-79%）的肿瘤强烈且弥漫地表达ERCC 1。使用逻辑回归方法，与68例ERCC 1高表达患者相比，28例（29%）低水平表达ERCC 1的肿瘤患者从化疗客观反应中获益的几率高4倍（比值比，4.3; 95%置信区间，1.4-13.4; P = 0.01）。ERCC 1和p53状态，但不是它们的相互作用，是肿瘤反应的独立预测因子。在校正了年龄、TNM分期、肿瘤分化和肿瘤定位的考克斯比例风险模型中，ERCC 1低表达与癌症死亡风险降低相关（风险比，0.42; 95%可信区间，0.20-0.90; P = 0.04），而p53状态无预后价值。我们的研究结果表明，ERCC 1低表达的患者比ERCC 1高表达的患者更容易从顺铂诱导化疗中获益。
Purpose: To assess the correlation of excision repair cross complementation group 1 (ERCC1) immunohistochemical expression with objective tumor response and cancer-specific survival in patients with locally advanced head and neck squamous cell carcinoma treated with cisplatin-based induction chemotherapy.Experimental Design: The initial cohort was composed of 107 patients who were treated from 1992 to 1996 by an induction chemotherapy regimen for locally advanced head and neck squamous cell carcinoma. p53 mutations had previously been studied. Pretherapeutic biopsy samples from 96 patients with a known tumor response were available. Two independent observers blinded to clinical annotations evaluated ERCC1 immunohistochemical expression.Results: Of 96 patients, 68 (71%; 95% confidence interval, 61-79%) had tumors that expressed ERCC1 intensively and diffusely. Using the logistic regression method, the 28 (29%) patients with tumors expressing ERCC1 at lower levels had a 4-fold greater odds of benefiting from an objective response to chemotherapy (odds ratio, 4.3; 95% confidence interval, 1.4-13.4; P = 0.01) compared with the group of 68 patients with high ERCC1 expression. ERCC1 and p53 status, but not their interaction, were independent predictors of tumor response. In a Cox proportional hazard model adjusted on age, TNM stage, tumor differentiation, and tumor localization, ERCC1 low expression was associated with a lower risk of cancer death (risk ratio, 0.42; 95% confidence interval, 0.20-0.90; P = 0.04) whereas p53 status had no prognostic value.Conclusion: Our results suggest that those patients characterized by low ERCC1 expression are more likely to benefit from cisplatin induction chemotherapy compared with patients with high ERCC1 expression.