Division of Epidemiology, Health Sciences Research, Mayo Clinic, Rochester, Minnesota 55905, USA.
J Thorac Oncol. 2012 Jan;7(1):90-7. doi: 10.1097/JTO.0b013e31823c5c32.
The EML4-anaplastic lymphoma kinase (ALK) translocation is a recognized oncogenic driver in non-small cell lung cancer. We investigated immunohistochemistry (IHC) screening with fluorescence in situ hybridization (FISH) confirmation for ALK detection and estimated the prevalence of ALK positivity in our patient cohort of never-smokers, together with differences in clinical outcomes and prognostic factors for patients with ALK-positive and ALK-negative tumors.
We designed a three-phase study (training, validation, and testing) in 300 never-smokers with lung adenocarcinoma from the observational Mayo Clinic Lung Cancer Cohort. Tumor samples were tested using IHC and FISH, and concordance between the methods was assessed. Clinical outcomes were assessed via 5-year progression- or recurrence-free survival from diagnosis. Prognostic factors for ALK-positive tumors and metastases were also investigated.
ALK-positive patients were significantly (p < 0.05) younger and had higher grade tumors than ALK-negative patients. ALK positivity was 12.2% by IHC and confirmed at 8.2% of tumors by FISH, with complete concordance between IHC 3+/0 and FISH+/- assessments, respectively. Five-year risk of progression or recurrence was doubled for patients with ALK-positive compared with ALK-negative tumors; ALK-positive tumors also appeared to be associated with a higher risk of brain and liver metastases.
Our findings suggest that ALK positivity is associated with a significantly poor outcome in nonsmoking-related adenocarcinoma and that ALK-positive tumors may be associated with an increased risk of brain and liver metastases compared with ALK-negative disease. Consequently, an unmet medical need exists in ALK-positive lung cancer patients, and effective ALK-specific therapies are needed.
EML4-间变性淋巴瘤激酶（ALK）易位是一种公认的非小细胞肺癌致癌驱动因素。我们通过荧光原位杂交（FISH）确认免疫组织化学（IHC）筛查来检测 ALK，并评估了我们从不吸烟的患者队列中 ALK 阳性的患病率，以及 ALK 阳性和 ALK 阴性肿瘤患者的临床结局和预后因素的差异。
我们在观察性梅奥诊所肺癌队列中设计了一项针对从不吸烟的肺腺癌患者的 300 例的三阶段研究（培训、验证和测试）。使用 IHC 和 FISH 测试肿瘤样本，并评估两种方法之间的一致性。通过诊断后 5 年的无进展或无复发生存来评估临床结局。还研究了 ALK 阳性肿瘤和转移的预后因素。
ALK 阳性患者明显（p < 0.05）年轻，肿瘤分级更高。IHC 检测的 ALK 阳性率为 12.2%，FISH 检测的阳性率为 8.2%，IHC 3+/0 和 FISH +/-评估之间具有完全一致性。与 ALK 阴性肿瘤相比，ALK 阳性肿瘤患者的进展或复发风险增加了一倍；ALK 阳性肿瘤似乎也与脑转移和肝转移的风险增加有关。
我们的研究结果表明，ALK 阳性与非吸烟相关性腺癌患者的预后显著不良相关，与 ALK 阴性疾病相比，ALK 阳性肿瘤可能与脑转移和肝转移的风险增加有关。因此，ALK 阳性肺癌患者存在未满足的医疗需求，需要有效的 ALK 特异性治疗。
