Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
PLoS One. 2013 Jul 26;8(7):e69016. doi: 10.1371/journal.pone.0069016. Print 2013.
Approximately 3-7% of non-small cell lung cancers harbor an anaplastic lymphoma kinase (ALK) gene fusion, constituting a new molecular subtype of lung cancer that responds to crizotinib, an ALK inhibitor. Although previous studies have evaluated ALK-rearranged lung cancers, the comprehensive analysis of lung cancer in Chinese has not well assessed. Herein, we identified 44 cases of ALK-rearranged samples by fluorescent in-situ hybridization (FISH), immunohistochemistry (IHC), and reverse transcription polymerase chain reaction (RT-PCR) in a large number of surgically resected lung cancers. All 44 ALK-rearranged lung cancers were adenocarcinomas, with 2 cases having additional focal squamous components. The goal was to analyse the clinicopathological features of ALK-rearranged lung adenocarcinomas. Our data showed that a cribriform structure, prominent extracellular mucus and any type of mucous cell pattern may be either sensitive or specific to predict an ALK rearrangement. We used FISH as the standard detection method. We compared the ALK rearrangement accuracy of FISH, RT-PCR and IHC. RT-PCR could define both the ALK fusion partner and the fusion variant, but seemed unable to detect all translocations involving the ALK gene. It is noteworthy that IHC using the D5F3 antibody (Cell Signaling Technology) showed higher sensitivity and specificity than the ALK1 antibody (Dako). Therefore, we conclude that IHC remains a cost-effective and efficient technique for diagnosing ALK rearrangements and that D5F3 can be the optimal screening antibody in clinical practice.
大约 3-7%的非小细胞肺癌存在间变性淋巴瘤激酶 (ALK) 基因融合，构成了一种对 ALK 抑制剂克唑替尼有反应的肺癌新分子亚型。尽管之前的研究已经评估了 ALK 重排的肺癌，但对中国肺癌的全面分析尚未得到很好的评估。在此，我们通过荧光原位杂交 (FISH)、免疫组织化学 (IHC) 和逆转录聚合酶链反应 (RT-PCR) 在大量手术切除的肺癌中鉴定了 44 例 ALK 重排样本。所有 44 例 ALK 重排肺癌均为腺癌，其中 2 例有额外的局灶性鳞状成分。目的是分析 ALK 重排肺腺癌的临床病理特征。我们的数据表明，筛状结构、突出的细胞外黏液和任何类型的黏液细胞模式可能对预测 ALK 重排具有敏感性或特异性。我们使用 FISH 作为标准检测方法。我们比较了 FISH、RT-PCR 和 IHC 检测 ALK 重排的准确性。RT-PCR 可以定义 ALK 融合伙伴和融合变体，但似乎无法检测到所有涉及 ALK 基因的易位。值得注意的是，使用 D5F3 抗体（Cell Signaling Technology）的 IHC 显示出比 ALK1 抗体（Dako）更高的敏感性和特异性。因此，我们得出结论，IHC 仍然是诊断 ALK 重排的一种具有成本效益和高效的技术，并且 D5F3 可以成为临床实践中的最佳筛选抗体。
