Department of Pathology, Aberdeen University Medical School, Aberdeen Royal Infirmary, Aberdeen, UK
Laboratorio de Dianas Terapéuticas, Hospital Universitario HM Sanchinarro, Madrid, Spain.
Ann Oncol. 2016 Sep;27 Suppl 3:iii16-iii24. doi: 10.1093/annonc/mdw302.
The evolution of personalised medicine in lung cancer has dramatically impacted diagnostic pathology. Current challenges centre on the growing demands placed on small tissue samples by molecular diagnostic techniques. In this review, expert recommendations are provided regarding successful identification of anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC). Steps to correctly process and conserve tumour tissue during diagnostic testing are essential to ensure tissue availability. For example, storing extra tissue sections ready for molecular diagnostic steps allows faster testing and preserves tissue. Fluorescence in situ hybridisation (FISH) is commonly used to detect ALK rearrangements, with most laboratories favouring screening by immunohistochemistry followed by a confirmatory FISH assay. Reverse transcription-polymerase chain reaction can also identify ALK fusion gene mRNA transcripts but can be limited by the quality of RNA and the risk that rare fusion variants may not be captured. Next-generation sequencing (NGS) technology has recently provided an alternative method for detecting ALK rearrangements. While current experience is limited, NGS is set to become the most efficient approach as an increasing number of genetic abnormalities is required to be tested. Upfront, reflex testing for ALK gene rearrangement should become routine as ALK tyrosine kinase inhibitor therapy moves into the first-line setting. Guidelines recommend that EGFR and ALK tests are carried out in parallel on all confirmed and potential adenocarcinomas, and this is more efficient in terms of tissue usage and testing turnaround time for both of these actionable gene alterations. The practice of sequential testing is not recommended. Identification of ALK rearrangements is now essential for the diagnosis of NSCLC, underpinned by the benefits of ALK inhibitors. As scientific understanding and diagnostic technology develops, ALK testing will continue to be an evolving and challenging paradigm.
个性化医学在肺癌中的发展对诊断病理学产生了重大影响。当前的挑战集中在分子诊断技术对小组织样本的需求不断增长。在这篇综述中，专家就成功识别间变性淋巴瘤激酶（ALK）重排的非小细胞肺癌（NSCLC）提供了建议。在诊断测试过程中，正确处理和保存肿瘤组织的步骤对于确保组织可用性至关重要。例如，存储额外的组织切片以备分子诊断步骤使用，可以加快测试速度并保存组织。荧光原位杂交（FISH）常用于检测 ALK 重排，大多数实验室倾向于先用免疫组织化学进行筛选，然后用 FISH 检测进行确认。逆转录聚合酶链反应（RT-PCR）也可用于识别 ALK 融合基因 mRNA 转录本，但可能受到 RNA 质量的限制，并且存在稀有融合变体可能无法捕获的风险。下一代测序（NGS）技术最近提供了一种检测 ALK 重排的替代方法。虽然目前的经验有限，但随着需要测试的遗传异常数量的增加，NGS 将成为最有效的方法。由于 ALK 酪氨酸激酶抑制剂治疗已进入一线治疗，因此应将 ALK 基因重排的即时检测作为常规检测。指南建议在所有确诊和潜在的腺癌上同时进行 EGFR 和 ALK 检测，这对于这两种可靶向基因改变的组织使用和测试周转时间都更有效率。不建议进行顺序测试。识别 ALK 重排现在对于 NSCLC 的诊断至关重要，ALK 抑制剂带来了获益。随着科学认识和诊断技术的发展，ALK 检测将继续成为一个不断发展和具有挑战性的范例。
