头颈部复发或转移性鳞状细胞癌患者中表皮生长因子受体（EGFR）III型变体、人乳头瘤病毒（HPV）、p16、c-间质-上皮转化因子（c-MET）、EGFR基因拷贝数与EGFR抑制剂反应之间的关联。

The association between EGFR variant III, HPV, p16, c-MET, EGFR gene copy number and response to EGFR inhibitors in patients with recurrent or metastatic squamous cell carcinoma of the head and neck.

作者信息

Chau Nicole G, Perez-Ordonez Bayardo, Zhang Katherine, Pham Nhu-An, Ho James, Zhang Tong, Ludkovski Olga, Wang Lisa, Chen Eric X, Tsao Ming-Sound, Kamel-Reid Suzanne, Siu Lillian L

机构信息

Division of Medical Oncology and Hematology, Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada.

出版信息

Head Neck Oncol. 2011 Feb 27;3:11. doi: 10.1186/1758-3284-3-11.

DOI:10.1186/1758-3284-3-11

PMID:21352589

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3052237/

Abstract

BACKGROUND

We examine the potential prognostic and predictive roles of EGFR variant III mutation, EGFR gene copy number (GCN), human papillomavirus (HPV) infection, c-MET and p16INK4A protein expression in recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN).

METHODS

We analyzed the archival tumor specimens of 53 patients who were treated in 4 phase II trials for R/M SCCHN. Two trials involved the EGFR inhibitor erlotinib, and 2 trials involved non-EGFR targeted agents. EGFRvIII mutation was determined by quantitative RT-PCR, HPV DNA by Linear Array Genotyping, p16 and c-MET protein expression by immunohistochemistry, and EGFR GCN by FISH.

RESULTS

EGFRvIII mutation, detected in 22 patients (42%), was associated with better disease control, but no difference was seen between erlotinib-treated versus non-erlotinib treated patients. EGFRvIII was not associated with TTP or OS. The presence of HPV DNA (38%), p16 immunostaining (32%), c-MET high expression (58%) and EGFR amplification (27%), were not associated with response, TTP or OS.

CONCLUSION

EGFRvIII mutation, present in about 40% of SCCHN, appears to be an unexpected prognostic biomarker associated with better disease control in R/M SCCHN regardless of treatment with erlotinib. Larger prospective studies are required to validate its significance.

摘要

背景

我们研究了表皮生长因子受体III型变异（EGFRvIII）突变、表皮生长因子受体（EGFR）基因拷贝数（GCN）、人乳头瘤病毒（HPV）感染、c-MET及p16INK4A蛋白表达在复发性或转移性头颈部鳞状细胞癌（R/M SCCHN）中的潜在预后及预测作用。

方法

我们分析了53例在4项II期试验中接受治疗的R/M SCCHN患者的存档肿瘤标本。两项试验涉及EGFR抑制剂厄洛替尼，两项试验涉及非EGFR靶向药物。通过定量逆转录聚合酶链反应（RT-PCR）检测EGFRvIII突变，通过线性阵列基因分型检测HPV DNA，通过免疫组织化学检测p16和c-MET蛋白表达，通过荧光原位杂交（FISH）检测EGFR GCN。

结果

在22例患者（42%）中检测到EGFRvIII突变，其与更好的疾病控制相关，但在厄洛替尼治疗组与非厄洛替尼治疗组患者之间未观察到差异。EGFRvIII与疾病无进展生存期（TTP）或总生存期（OS）无关。HPV DNA的存在（38%）、p16免疫染色（32%）、c-MET高表达（58%）及EGFR扩增（27%）与反应、TTP或OS均无关。