Temam Stephane, Kawaguchi Hidetoshi, El-Naggar Adel K, Jelinek Jaroslav, Tang Hongli, Liu Diane D, Lang Wenhua, Issa Jean-Pierre, Lee J Jack, Mao Li
Molecular Biology Laboratory and Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
J Clin Oncol. 2007 Jun 1;25(16):2164-70. doi: 10.1200/JCO.2006.06.6605.
Overexpression of epidermal growth factor receptor (EGFR) is common in head and neck squamous cell carcinoma (HNSCC). Recent studies showed that EGFR inhibitors are effective for patients with HNSCC. This study analyzed the genetic nature of EGFR gene in HNSCC and its clinical correlations.
The EGFR gene copy numbers in 134 HNSCC tumors were determined using quantitative real-time polymerase chain reaction. The status of EGFR gene copy numbers was analyzed with clinical parameters including clinical outcome. Mutation status of EGFR exons 18, 19, and 21 was determined in the HNSCC tumors.
Aberrant EGFR copy numbers were found in 32 (24%) of 134 tumors, including 22 (17%) with increased copy number and 10 (7%) with decreased copy number. Patients whose tumors had EGFR copy number alterations (particularly patients with increased copy numbers) had significantly poorer overall, cancer-specific, and disease-free survivals compared with patients with normal copy numbers (P < .0001). At 5 years after initial diagnosis, 20 (91%) of the 22 patients with increased copy numbers died of disease compared with 30 (29%) of the 102 patients with normal copy number. No mutations on EGFR exons 18, 19, and 21 were detected in any of the tumors.
A subset of HNSCC manifests EGFR copy number alterations, and this is associated with a poor clinical outcome, suggesting a biologic role of the alterations. The rare mutation or small deletion at EGFR exons 18 to 21 indicates a minimal role of these events in HNSCC.
表皮生长因子受体（EGFR）的过表达在头颈部鳞状细胞癌（HNSCC）中很常见。最近的研究表明，EGFR抑制剂对HNSCC患者有效。本研究分析了HNSCC中EGFR基因的遗传特性及其临床相关性。
使用定量实时聚合酶链反应测定134例HNSCC肿瘤中EGFR基因的拷贝数。分析EGFR基因拷贝数状态与包括临床结局在内的临床参数之间的关系。测定HNSCC肿瘤中EGFR第18、19和21外显子的突变状态。
在134例肿瘤中的32例（24%）发现EGFR拷贝数异常，其中22例（17%）拷贝数增加，10例（7%）拷贝数减少。与拷贝数正常的患者相比，肿瘤有EGFR拷贝数改变的患者（尤其是拷贝数增加的患者）的总生存期、癌症特异性生存期和无病生存期明显更差（P <.0001）。在初次诊断后5年，22例拷贝数增加的患者中有20例（91%）死于疾病，而拷贝数正常的102例患者中有30例（29%）死亡。在任何肿瘤中均未检测到EGFR第18、19和21外显子的突变。
一部分HNSCC表现出EGFR拷贝数改变，这与不良临床结局相关，提示这些改变具有生物学作用。EGFR第18至21外显子的罕见突变或小缺失表明这些事件在HNSCC中的作用极小。
