p95HER2 Truncated Form in Resected Non-small Cell Lung Cancer
p95HER2 Truncated Form in Resected Non-small Cell Lung Cancer
复制标题
DOI：
10.1097/jto.0b013e318249e13f
复制
发表时间：
2012-03-01
影响因子：
20.4
通讯作者：
Varella-Garcia, Marileila
中科院分区：
文献类型：
--
作者：
Cappuzzo, Federico;Cho, Yong Gon;Varella-Garcia, Marileila
前言：最近的研究表明，人表皮生长因子受体2(HER2)的NH2末端截短形式的p95HER2可以产生对抗HER2的单抗(HER2-MAb)的抵抗。本研究的目的是根据HER2基因拷贝数(GCN)和HER2突变情况探讨p95HER2在非小细胞肺癌(NSCLC)中的作用。将数据与荧光原位杂交(FISH)和HER2突变评估的HER2 GCN进行关联。结果：431例P95HER2阳性患者中，33例(7.6%)P95HER2阳性。在439例患者中，HER2 GCN可评价，60例GCN增加(至少40%的细胞中至少有4个拷贝)，其中22例(5.0%)表现为基因扩增(GA)。在22例HER2扩增的患者中，只有1例P95HER2+。为了进一步研究在存在基因突变的情况下受体是否被截断，除了研究队列外，我们还分析了8例携带HER2突变的非小细胞肺癌样本中p95HER2的状态，其中只有1例导致了p95HER2+。在整个人群中，p95HER2-患者的死亡风险高于p95HER2+患者(风险比=1.4，p=0.2)。使用和不使用HER2 GA的患者的生存时间没有差异(中位数分别为38个月和41个月，p=0.46)。HER2GA与EGFR和MET GA显著相关，对生存率无明显影响。结论：HER2截短和HER2增加GCN对NSCLC患者的预后无明显影响。P95HER2在显示HER2基因扩增或突变的个体中是一种非常罕见的事件。
Introduction: Recent studies suggested that p95HER2, the NH2-terminally truncated form of human epidermal growth factor receptor 2 (HER2), could confer resistance to monoclonal antibodies against HER2 (HER2-mab). The aim of this study was to investigate the role of p95HER2 according to HER2 gene copy number (GCN) and HER2 mutation in non-small cell lung cancer (NSCLC).Methods: The study included 447 resected NSCLC patients evaluated for P95HER2 status by immunofluorescence. Data were correlated with HER2 GCN evaluated by fluorescence in situ hybridization (FISH) and HER2 mutations. Tumors were scored as positive for p95HER2 expression if any cytoplasmic staining was detected.Results: P95HER2 was successfully evaluated in 431 patients and was positive (p95HER2+) in 33 (7.6%) cases. HER2 GCN was evaluable in 439 patients, and increased GCN (at least four copies in at least 40% cells) was found in 60 cases, of which 22 (5.0%) displayed gene amplification (GA). Among the 22 patients with HER2 amplification, only one resulted P95HER2+. To further investigate whether the receptor is truncated in presence of gene mutation, in addition to the study cohort, we analyzed p95HER2 status in eight NSCLC samples harboring HER2 mutation, and only one case resulted p95HER2+. In the whole population, p95HER2- patients had numerically higher risk of death than p95HER2+ (hazard ratio = 1.4, p = 0.2). No difference in survival was observed between patients with or without HER2 GA (median 38 versus 41 months, p = 0.46). HER2 GA was significantly associated with EGFR and MET GA, with no effect on survival.Conclusions: HER2 truncation and HER2 increased GCN are not prognostic in resected NSCLC. P95HER2 is a very rare event in individuals displaying HER2 gene amplification or mutation.