Supplementary Material for: Molecular Epidemiology of ALK Rearrangements in Advanced Lung Adenocarcinoma in Latin America

Objective: Latin American countries are heterogeneous in terms of lung cancer incidence and exposure to potential carcinogens. We evaluated the frequency and clinical characteristics of ALK rearrangements (ALKr) in Latin America. Methods: A total of 5,130 lung cancer patients from 10 Latin American countries were screened for inclusion. ALKr detection was performed by fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) to assess method variability. Demographic and clinicopathologic characteristics were analyzed. Results: Among the 5,130 patients screened, 8.4% (n = 433) had nonevaluable FISH tests. Evaluable FISH analyses revealed positive ALKr in 6.8% (320/4,697) of the study population, which included patients from 9 countries. ALKr distribution for each country was: Mexico 7.6% (79/1,034), Colombia 4.1% (10/242), Argentina 6.0% (153/2,534), Costa Rica 9.5% (13/137), Panama 4.4% (5/114), Uruguay 5.4% (2/37), Chile 8.6% (16/185), Venezuela 8.9% (13/146), and Peru 10.8% (29/268). RT-PCR showed high positive (83.6%) and negative (99.7%) predictive values when compared to the gold standard FISH. In contrast, IHC only showed a high negative predictive value (94.6%). Conclusions: Although there is a clear country and continental variability in terms of ALKr frequency, this difference is not significant and the overall incidence of ALKr in Latin America does not differ from the rest of the world.研究背景与目的：拉丁美洲各国在肺癌发病率与潜在致癌物暴露层面存在显著异质性。本研究旨在评估拉丁美洲地区间变性淋巴瘤激酶重排（ALK rearrangements, ALKr）的发生频率及临床特征。 方法：本研究纳入来自10个拉丁美洲国家的共计5130例肺癌患者开展筛查。采用荧光原位杂交（fluorescence in situ hybridization, FISH）、免疫组化（immunohistochemistry, IHC）及实时逆转录聚合酶链反应（real-time reverse transcriptase-polymerase chain reaction, RT-PCR）进行ALKr检测，以评估不同检测方法的变异程度；同时分析受试者的人口学与临床病理特征。 结果：在纳入筛查的5130例患者中，8.4%（n=433）的FISH检测结果不可评估。可评估的FISH检测结果显示，研究人群中6.8%（320/4697）存在ALKr阳性，覆盖9个国家的患者。各国ALKr分布情况如下：墨西哥7.6%（79/1034）、哥伦比亚4.1%（10/242）、阿根廷6.0%（153/2534）、哥斯达黎加9.5%（13/137）、巴拿马4.4%（5/114）、乌拉圭5.4%（2/37）、智利8.6%（16/185）、委内瑞拉8.9%（13/146）以及秘鲁10.8%（29/268）。与金标准FISH相比，RT-PCR的阳性预测值达83.6%，阴性预测值达99.7%；与之相对，免疫组化仅表现出较高的阴性预测值（94.6%）。 结论：尽管拉丁美洲地区各国间ALKr的发生频率存在明显的地域差异，但该差异并无统计学显著性，且拉丁美洲地区ALKr的总体发病率与全球其他地区并无显著差异。