Reliable Entity Subtyping in Non-small Cell Lung Cancer by Matrix-assisted Laser Desorption/Ionization Imaging Mass Spectrometry on Formalin-fixed Paraffin-embedded Tissue Specimens
Reliable Entity Subtyping in Non-small Cell Lung Cancer by Matrix-assisted Laser Desorption/Ionization Imaging Mass Spectrometry on Formalin-fixed Paraffin-embedded Tissue Specimens
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DOI：
10.1074/mcp.m115.057513
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发表时间：
2016-10-01
影响因子：
7
通讯作者：
Weichert, Wilko
中科院分区：
文献类型：
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作者：
Kriegsmann, Mark;Casadonte, Rita;Weichert, Wilko
将非小细胞肺癌（NSCLC）分为腺癌（ADC）和鳞状细胞癌（SqCC）的组织学亚型与治疗分层最相关。然而，目前基于活检的免疫组织化学（IHC）分型方法是不完善的，因此需要可靠的亚型分析方法。我们分析了福尔马林固定石蜡包埋的NSCLC组织核心基质辅助激光解吸/电离（MALDI）成像的组织微阵列，以确定和验证歧视MALDI成像轮廓NSCLC亚型。使用110个ADC和98个SqCC来训练线性判别分析（LDA）模型。在58个ADC和60个SqCC的单独组上验证结果。通过串联质谱法鉴定选择的差异表达蛋白，并通过IHC进行验证。LDA分类模型包含339 m/z值。在验证队列中，117例（99.1%）组织芯的MALDI分类与切除标本的病理诊断一致。总体而言，合并队列中的3例病例不一致，重新评价后，2例最初被病理学错误分类，而1例被MALDI错误分类。差异表达肽的鉴定检测了众所周知的IHC鉴别物（CK 5、CK 7），但也检测了不太熟知的差异表达蛋白（CK 15、HSP 27）。总之，作为小活检等效物的NSCLC组织芯的MALDI成像能够以非常高的准确度区分肺ADC和SqCC。此外，用单载玻片MALDI方法代替多载玻片IHC也可以为后续的预测性分子检测保存组织。因此，我们主张在实体瘤分型中采用常规的MALDI成像诊断实施策略。
Histopathological subtyping of non-small cell lung cancer (NSCLC) into adenocarcinoma (ADC), and squamous cell carcinoma (SqCC) is of utmost relevance for treatment stratification. However, current immunohistochemistry (IHC) based typing approaches on biopsies are imperfect, therefore novel analytical methods for reliable subtyping are needed. We analyzed formalin-fixed paraffin-embedded tissue cores of NSCLC by Matrix-assisted laser desorption/ionization (MALDI) imaging on tissue microarrays to identify and validate discriminating MALDI imaging profiles for NSCLC subtyping. 110 ADC and 98 SqCC were used to train a Linear Discriminant Analysis (LDA) model. Results were validated on a separate set of 58 ADC and 60 SqCC. Selected differentially expressed proteins were identified by tandem mass spectrometry and validated by IHC. The LDA classification model incorporated 339 m/z values. In the validation cohort, in 117 cases (99.1%) MALDI classification on tissue cores was in accordance with the pathological diagnosis made on resection specimen. Overall, three cases in the combined cohorts were discordant, after reevaluation two were initially misclassified by pathology whereas one was classified incorrectly by MALDI. Identification of differentially expressed peptides detected well-known IHC discriminators (CK5, CK7), but also less well known differentially expressed proteins (CK15, HSP27). In conclusion, MALDI imaging on NSCLC tissue cores as small biopsy equivalents is capable to discriminate lung ADC and SqCC with a very high accuracy. In addition, replacing multislide IHC by an one-slide MALDI approach may also save tissue for subsequent predictive molecular testing. We therefore advocate to pursue routine diagnostic implementation strategies for MALDI imaging in solid tumor typing.