Department of Medicine II, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
J Proteome Res. 2010 Dec 3;9(12):6317-22. doi: 10.1021/pr100573s. Epub 2010 Nov 8.
HER2-testing in breast and gastric cancers is mandatory for the treatment with trastuzumab. We hypothesized that imaging mass spectrometry (IMS) of breast cancers may be useful for generating a classifier that may determine HER2-status in other cancer entities irrespective of primary tumor site. A total of 107 breast (n = 48) and gastric (n = 59) cryo tissue samples was analyzed by IMS (HER2 was present in 29 cases). The obtained proteomic profiles were used to create HER2 prediction models using different classification algorithms. A breast cancer proteome derived classifier, with HER2 present in 15 cases, correctly predicted HER2-status in gastric cancers with a sensitivity of 65% and a specificity of 92%. To create a universal classifier for HER2-status, breast and nonbreast cancer samples were combined, which increased sensitivity to 78%, and specificity was 88%. Our proof of principle study provides evidence that HER2-status can be identified on a proteomic level across different cancer types suggesting that HER2 overexpression may constitute a unique molecular event independent of the tumor site. Furthermore, these results indicate that IMS may be useful for the determination of potential drugable targets, as it offers a quicker, cheaper, and more objective analysis than the standard HER2-testing procedures immunohistochemistry and fluorescence in situ hybridization.
曲妥珠单抗的治疗必须进行 HER2 检测，无论是乳腺癌还是胃癌。我们假设，乳腺癌的成像质谱（IMS）可能有助于生成一个分类器，该分类器可确定其他癌症实体的 HER2 状态，而与原发肿瘤部位无关。共分析了 107 例乳腺癌（n = 48）和胃癌（n = 59）冷冻组织样本（29 例存在 HER2）。使用不同的分类算法，对获得的蛋白质组图谱进行 HER2 预测模型的创建。使用源自乳腺癌的分类器，其中存在 15 例 HER2，对胃癌的 HER2 状态进行了正确预测，敏感性为 65%，特异性为 92%。为了创建 HER2 状态的通用分类器，将乳腺癌和非乳腺癌样本合并，这将敏感性提高到 78%，特异性为 88%。我们的原理验证研究提供了证据，表明可以在不同癌症类型的蛋白质水平上识别 HER2 状态，这表明 HER2 过表达可能构成独立于肿瘤部位的独特分子事件。此外，这些结果表明，IMS 可能有助于确定潜在的可治疗靶点，因为与标准的 HER2 检测程序免疫组织化学和荧光原位杂交相比，它提供了更快、更便宜和更客观的分析。
