FLUORESCENCE IN SITU HYBRIDIZATION GENE AMPLIFICATION ANALYSIS OF EGFR AND HER2 IN PATIENTS WITH MALIGNANT SALIVARY GLAND TUMORS TREATED WITH LAPATINIB
FLUORESCENCE IN SITU HYBRIDIZATION GENE AMPLIFICATION ANALYSIS OF EGFR AND HER2 IN PATIENTS WITH MALIGNANT SALIVARY GLAND TUMORS TREATED WITH LAPATINIB
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DOI：
10.1002/hed.21052
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发表时间：
2009-08-01
影响因子：
2.9
通讯作者：
Siu, Lillian L.
中科院分区：
文献类型：
--
作者：
Vidal, Laura;Tsao, Ming S.;Siu, Lillian L.
背景分析表皮生长因子受体（EGFR）和人表皮生长因子受体2（HER 2）的基因扩增状态，并与EGFR/HER 2酪氨酸激酶双重抑制剂拉帕替尼治疗的进行性恶性涎腺肿瘤（MSGT）患者的临床结局相关。在20例腺样囊性癌（ACC）和17例非ACC患者的存档肿瘤标本中成功进行了EGFR和HER 2基因扩增的荧光原位杂交（FISH）分析，所有患者均接受拉帕替尼治疗。对于ACC，未检测到EGFR或HER 2扩增。对于非ACC，未检测到EGFR基因扩增，但3例患者（18%）的HER 2扩增，所有患者的存档标本中EGFR和HER 2免疫组织化学（IHC）染色均为3+。其中2例患者的至进展时间（TTP）分别为8.3个月和18.4个月。有趣的是，低和高HER 2/染色体特异性着丝粒计数探针（CEP）17比率的患者比ACC和非AAC亚型的中等比率的患者TTP延长。HER 2与CEP 17 FISH比值可以预测哪些MSGT患者从拉帕替尼中获益的可能性增加。HER 2：CEP 17比值作为拉帕替尼疗效的预测标志物的发现值得进一步研究。(C)2009 Wiley Periodicals，Inc.头颈部31：1006-1012，2009年
Background. Gene amplification status of the epidermal growth factor receptor (EGFR) and the human epidermal growth factor receptor 2 (HER2) were analyzed and correlated with clinical outcome in patients with progressive malignant salivary glands tumors (MSGT) treated with the dual EGFR/Her2 tyrosine kinase inhibitor lapatinib.Methods. Fluorescence in situ hybridization (FISH) analysis for both EGFR and HER2 gene amplification was performed successfully in the archival tumor specimens of 20 patients with adenoid cystic carcinomas (ACC) and 17 patients with non-ACC, all treated with lapatinib.Results. For ACC, no EGFR or HER2 amplifications were detected. For non-ACC, no EGFR gene amplifications were detected but 3 patients (18%) were HER2 amplified and all had stained 3+ for both EGFR and HER2 by immunohistochemistry (IHC) in their archival specimens. Two of these patients had time-to-progression (TTP) durations of 8.3 months and 18.4 months, respectively. Interestingly, patients with low and high HER2/chromosome-specific centromeric enumeration probe (CEP) 17 ratio had a prolonged TTP than those with moderate ratios for both ACC and non-AAC subtypes.Conclusions. HER2 to CEP17 FISH ratio may predict which patients with MSGT have an increased likelihood to benefit from lapatinib. The finding of HER2:CEP17 ratio as a predictive marker of efficacy to lapatinib warrants further investigation. (C) 2009 Wiley Periodicals, Inc. Head Neck 31: 1006-1012, 2009