Robesova Blanka, Bajerova Monika, Hausnerova Jitka, Skrickova Jana, Tomiskova Marcela, Dvorakova Dana
Department of Internal Medicine-Hematology and Oncology, Masaryk University and University Hospital Brno, Brno, Czech Republic.
Department of Internal Medicine-Hematology and Oncology, Masaryk University and University Hospital Brno, Brno, Czech Republic.
Lung Cancer. 2015 Mar;87(3):318-20. doi: 10.1016/j.lungcan.2015.01.002. Epub 2015 Jan 10.
We herein present a rare case of an EML4-ALK positive patient. A 61-year-old man was diagnosed with locoregional non-small cell lung cancer (NSCLC). No EGFR mutations were detected, and therefore the ALK rearrangement was evaluated using immunohistochemistry (IHC), fluorescence in situ hybridization (FISH) and the reverse transcription PCR (RT-PCR) method for EML4-ALK. All methods showed a positive result and, therefore, the patient was treated with crizotinib with a good therapeutic response. However, a detailed RT-PCR analysis and sequencing revealed an unexpected 138 bp insertion of attractin-like 1 (ATRNL1) gene into the EML4-ALK fusion gene. In our case, the positive therapeutic response suggests that ATRNL1 insertion does not affect EML4-ALK's sensitivity to crizotinib. This case shows great EML4-ALK heterogeneity and also that basic detection methods (IHC, FISH) cannot fully specify ALK rearrangement but in many cases a full specification seems to be important for an effective TKI indication, and sequencing ALK variants might contribute to optimized patient selection.
我们在此报告一例罕见的EML4-ALK阳性患者。一名61岁男性被诊断为局部非小细胞肺癌（NSCLC）。未检测到EGFR突变，因此使用免疫组织化学（IHC）、荧光原位杂交（FISH）以及针对EML4-ALK的逆转录PCR（RT-PCR）方法评估ALK重排。所有方法均显示阳性结果，因此该患者接受了克唑替尼治疗，治疗反应良好。然而，详细的RT-PCR分析和测序显示，吸引素样1（ATRNL1）基因意外地插入到EML4-ALK融合基因中138 bp。在我们的病例中，积极的治疗反应表明ATRNL1插入并不影响EML4-ALK对克唑替尼的敏感性。该病例显示出EML4-ALK具有很大的异质性，同时也表明基本检测方法（IHC、FISH）不能完全明确ALK重排，但在许多情况下，完整明确似乎对有效的酪氨酸激酶抑制剂（TKI）治疗指征很重要，对ALK变异体进行测序可能有助于优化患者选择。
