Immunohistochemical detection of EGFRvIII in high malignancy grade astrocytomas and evaluation of prognostic significance
Immunohistochemical detection of EGFRvIII in high malignancy grade astrocytomas and evaluation of prognostic significance
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DOI：
10.1093/jnen/63.7.700
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发表时间：
2004-07-01
影响因子：
3.2
通讯作者：
James, CD
中科院分区：
文献类型：
--
作者：
Aldape, KD;Ballman, K;James, CD
本研究的目的是建立一种准确、简便的检测表皮生长因子受体的免疫组织化学方法，并评价该方法在恶性星形细胞瘤中检测的预后意义。该方法的准确性是通过比较福尔马林固定和石蜡包埋的肿瘤切片中的VIII免疫反应性与从相应冰冻标本中提取的RNA的RT-PCR结果来确定的。在44例肿瘤中，有18例RT-PCR显示出VIII转录本，对匹配的福尔马林固定切片和石蜡包埋切片的IHC分析显示，这18例肿瘤中每一例都有EGFRvIII反应，另外还有1例该转录本阴性的肿瘤。在所有表达VIII的肿瘤中，EGFR扩增都很明显；15例缺乏EGFR扩增的肿瘤中，没有一例VIII转录本或VIII蛋白阳性。接下来对来自临床试验患者的大量间变性星形细胞瘤(AAs)和多形性胶质母细胞瘤(GBMs)进行了VIII表达的IHC分析，这些患者之前已经通过FISH检查了扩增的EGFR。在46例有EGFR扩增的肿瘤中，19例(41.3%)用免疫组织化学方法检出了VIII型基底膜，而在59例未扩增EGFR的肿瘤中，仅有3例(5.1%)检出。在14例EGFR扩增的AAS中，3例表达(21.4%)，49例未扩增的AAS中6例表达(12.2%)。基底膜和再生障碍性贫血患者的生存分析显示，VIII型表达与基底膜患者的生存期无关(p=0.84)，但与再生障碍性贫血患者的生存期降低(p=0.0016)密切相关。后者的发现，尽管很可能是由于VIII与AA患者年龄的增加有关，但表明VIII IHC将有助于识别和/或确认其临床行为与GBM一致的恶性星形细胞瘤的身份。
The purpose of this study was to establish an accurate and accessible immunohistochemical (IHC) method for detecting vIII Egf receptor and to assess the prognostic significance of the method as applied to the detection of vIII in malignant astrocytomas. The accuracy of the method was determined by comparing vIII immunoreactivity in formalin-fixed and paraffin-embedded tumor sections versus RT-PCR results from the analysis of RNA extracted from corresponding frozen specimens. RT-PCR revealed vIII transcript in 18 of 44 cases in this series, and IHC analysis of matched formalin-fixed and paraffin-embedded sections showed EGFRvIII reactivity in each of these 18 tumors, as well as 1 additional tumor that was negative for vIII transcript. EGFR amplification was evident in all tumors expressing vIII; none of the 15 tumors lacking amplified EGFR were positive for vIII transcript or vIII protein. IHC analysis for vIII expression was next applied to a large series of anaplastic astrocytomas (AAs) and glioblastoma multiforme (GBMs) from clinical trial patients with complete follow-up and that had been previously examined by FISH for amplified EGFR. Among the GBMs, vIII detection by IHC was determined in 19 of 46 cases (41.3%) with EGFR amplification, and in only 3 of 59 tumors lacking amplified EGFR (5.1%). Among the AAs, vIII expression was observed in 3 of 14 cases with amplified EGFR (21.4%) and in 6 of 49 cases without EGFR amplification (12.2%). GBM and AA patient survival analysis as a function of vIII expression showed contrasting results, with vIII positivity having no association with survival among GBM patients (p = 0.84), but being highly associated with reduced survival among AA patients (p = 0.0016). This latter finding, though quite possibly a result of vIII's association with increasing AA patient age, suggests that vIII IHC will be useful for identifying and/or confirming the identity of malignant astrocytomas whose clinical behavior is consistent with that of GBM.