Standardization of HER2 testing:: results of an international proficiency-testing ring study
Standardization of HER2 testing:: results of an international proficiency-testing ring study
复制标题
DOI：
10.1038/modpathol.3800774
复制
发表时间：
2007-05-01
期刊：
影响因子：
7.5
通讯作者：
van de Vijver, Marc J.
中科院分区：
文献类型：
--
作者：
Dowsett, Mitch;Hanna, Wedad M.;van de Vijver, Marc J.
乳腺癌中人表皮生长因子受体2(HER2)阳性是肿瘤侵袭性的预后因素，也是曲妥珠单抗(Herceptins)疗效的预测因素。在初诊时对所有乳腺癌患者进行早期和准确的HER2检测对于优化疾病治疗至关重要。常规的HER2检测，如免疫组织化学和荧光原位杂交(FISH)，受到实验室间差异的影响，实验室能力测试的验证对于提高标准化很重要。这项研究比较了五个国际病理学参考中心的免疫组织化学和FISH检测。每个中心在五轮测试中评估了20个免疫组织化学和20个鱼类乳腺癌样本。在每一轮中，一个中心选择两组四种不同的侵袭性肿瘤标本(A组用于免疫组织化学，B组用于FISH)，并以盲法将样本送到其他四个中心，同时保留样本供自己评估。结果由一名独立协调员进行分析。免疫组织化学结果显示，在HER2阳性或阴性的诊断水平上，这五个中心之间的任何一个样本都没有差异。然而，不同实验室之间的免疫组织化学评分存在差异。在20份标本中，4份为阴性(0/1+)，5份为阳性(3+)；8份为阴性或可疑(2+)，3份为阳性或可疑。在对11个可疑免疫组织化学病例中的9个进行FISH重新检测后，在18个样本中有15个(83%)获得了共识。对SET B样本的FISH分析结果显示，在20个样本中，有16个(80%)的中心之间存在一致性(6个阴性样本，10个阳性样本)。所有四个不协调的鱼标本至少有一个中心评分为HER2：CEP17比率在1.7-2.3范围内。模棱两可的免疫组织化学和边缘FISH案例很难解释，即使对于经验丰富和经过验证的实验室也是如此，这突出了质量控制程序的必要性。
Human epidermal growth factor receptor 2 (HER2) positivity in breast cancer is a prognostic factor regarding tumor aggressiveness and a predictive factor for response to trastuzumab (Herceptins). Early and accurate HER2 testing of all breast cancer patients at primary diagnosis is essential for optimal disease management. Routine HER2 tests, such as immunohistochemistry and fluorescence in situ hybridization (FISH), are subject to interlaboratory variation, and validation by laboratory proficiency testing is important to improve standardization. This study compared immunohistochemistry and FISH testing between five international pathology reference centers. Each center evaluated 20 immunohistochemistry and 20 FISH breast cancer specimens in five testing rounds. In each round, one center selected two sets of four different invasive tumor specimens ( set A for immunohistochemistry and set B for FISH) and sent samples to the other four centers in a blinded manner, while retaining samples for its own evaluation. Results were analyzed by an independent coordinator. With immunohistochemistry, there were no differences between the five centers for any of the specimens at the level of diagnostic decision (positive or negative HER2 status). However, differences between laboratories were observed in immunohistochemistry scoring. Of the 20 specimens, four were scored as negative (0/1+) and five as positive (3+) in all centers; eight were negative or equivocal (2+), and three positive or equivocal. After FISH retesting of nine of the 11 equivocal immunohistochemistry cases, consensus was achieved in 15 of 18 (83%) specimens. FISH analysis of set B specimens resulted in consensus between centers in 16 of 20 (80%) specimens (six negative and 10 positive). All four discordant FISH specimens were scored as having HER2:CEP17 ratios within the range 1.7-2.3 by at least one center. Equivocal immunohistochemistry and borderline FISH cases are difficult to interpret, even for highly experienced and validated laboratories, highlighting the need for quality-control procedures.