Mohamad N, Jayalakshmi P, Rhodes A, Liam C-K, Tan J-L, Yousoof S, Rajadurai P
a Department of Pathology, Faculty of Medicine , University of Malaya , Kuala Lumpur , Malaysia.
b Department of Medicine, Faculty of Medicine , University of Malaya , Kuala Lumpur , Malaysia.
Br J Biomed Sci. 2017 Oct;74(4):176-180. doi: 10.1080/09674845.2017.1331520. Epub 2017 Jul 13.
Non-small cell lung cancer (NSCLC) is a major cause of cancer-related death. Approximately 2-16% of NSCLC patients with wild-type epidermal growth factor receptor (EGFR) harbour anaplastic lymphoma kinase (ALK) mutations. Both EGFR and ALK mutations occur most commonly in Asian patients with NSCLC. As targeted therapy is available for NSCLC patients with these mutations, it is important to establish reliable assays and testing strategies to identify those most likely to benefit from this therapy.
Patients diagnosed with adenocarcinoma of the lung between 2010 and 2014 were tested for EGFR mutations. Of these, 92 cases were identified as EGFR wild type and suitable candidates for ALK testing utilising immunohistochemistry and the rabbit monoclonal antibody D5F3. The reliability of the IHC was confirmed by validating the results against those achieved by fluorescence in situ hybridisation (FISH) to detect ALK gene rearrangements.
Twelve (13%) cases were positive for ALK expression using immunohistochemistry. Of the 18 evaluable cases tested by FISH, there was 100% agreement with respect to ALK rearrangement/ALK expression between the assays, with 11 cases ALK negative and 7 cases ALK positive by both assays. ALK tumour expression was significantly more common in female compared to male patients (29.6% vs. 6.2%, P < 0.001), detected exclusively in patients that had never smoked (P < 0.001) and more frequently in metastases (22.7%) than in primary tumours (10%) (P = 0.047).
Detection of ALK expression by IHC is reliable and the most practical way of identifying NSCLC patients likely to benefit from crizotinib treatment.
非小细胞肺癌（NSCLC）是癌症相关死亡的主要原因。约2-16%野生型表皮生长因子受体（EGFR）的NSCLC患者存在间变性淋巴瘤激酶（ALK）突变。EGFR和ALK突变在亚洲NSCLC患者中最为常见。由于针对这些突变的NSCLC患者有靶向治疗可用，因此建立可靠的检测方法和测试策略以识别最可能从该治疗中获益的患者非常重要。
对2010年至2014年间诊断为肺腺癌的患者进行EGFR突变检测。其中，92例被确定为EGFR野生型，是使用免疫组织化学和兔单克隆抗体D5F3进行ALK检测的合适候选者。通过将免疫组化结果与荧光原位杂交（FISH）检测ALK基因重排的结果进行验证，确认了免疫组化的可靠性。
使用免疫组织化学检测，12例（13%）病例ALK表达呈阳性。在通过FISH检测的18例可评估病例中，两种检测方法在ALK重排/ALK表达方面完全一致，两种检测方法均显示11例ALK阴性，7例ALK阳性。与男性患者相比，ALK肿瘤表达在女性患者中明显更常见（29.6%对6.2%，P<0.001），仅在从不吸烟的患者中检测到（P<0.001），并且在转移灶中（22.7%）比在原发性肿瘤中（10%）更频繁（P=0.047）。
通过免疫组化检测ALK表达是可靠的，也是识别可能从克唑替尼治疗中获益的NSCLC患者的最实用方法。
