Zaric Bojan, Stojsic Vladimir, Panjkovic Milana, Tegeltija Dragana, Stepanov Vanesa, Kovacevic Tomi, Sarcev Tatjana, Radosavljevic Davorin, Milovancev Aleksandar, Adamidis Vasilis, Zarogoulidis Paul, Hohenforst-Schmidt Wolfgang, Trakada Georgia, Rapti Aggeliki, Perin Branislav
Institute for Pulmonary Diseases of Vojvodina, Faculty of Medicine, University of Novi Sad, Serbia.
Institute of Oncology and Radiology of Serbia, Belgrade, Serbia.
J Cancer. 2016 Oct 25;7(15):2207-2212. doi: 10.7150/jca.16768. eCollection 2016.
: The incidence of echinoderm microtubule-associated protein-like4-anaplastic lymphoma kinase (EML4-ALK) mutation among surgically treated patients with adenocarcinoma of the lung of the Eastern European ethnicity is underreported. The aim of this trial was the determination of EML4-ALK mutation frequency in investigated population, and the evaluation of correlations between lung adenocarcinoma subtype and clinical characteristics with mutation status. : This was a prospective trial which included 195 patients with adenocarcinoma of the lung who underwent surgical treatment. ALK mutation screening was performed by immunohistochemistry (IHC). IHC scores of 2+ and 3+ were regarded as positive. Confirmatory FISH was performed in all IHC positive and in 2:1 ratio in negative patients. : Overall ALK mutation rate established by IHC was 6.2%, while FISH confirmed rate of 5.1%. The FISH confirmed ALK positivity in 7.6% Hungarians, 5.5% Serbians, and 6.6% Slovakians. Acinar subtype of adenocarcinoma of the lung was significantly (p=0.02) related to EML4-ALK positive mutation status. Most of the patients were males (56.9%), smokers (50.8%), or former smokers (28.7%) with acinar (55.4%) or solid (35.9%) adenocarcinoma of the lung. Sensitivity and specificity of IHC were 100% and 98.9% respectively. : ALK mutation rate in surgically treated patients with adenocarcinoma of the lung was found to be 6.2% by IHC and 5.1% by FISH. Acinar subtype of the adenocarcinoma of the lung was significantly related to ALK positive mutation.
在接受手术治疗的东欧裔肺癌腺癌患者中,棘皮动物微管相关蛋白样4-间变性淋巴瘤激酶(EML4-ALK)突变的发生率报告不足。本试验的目的是确定研究人群中EML4-ALK突变频率,并评估肺腺癌亚型及临床特征与突变状态之间的相关性。
这是一项前瞻性试验,纳入了195例接受手术治疗的肺腺癌患者。通过免疫组织化学(IHC)进行ALK突变筛查。IHC评分为2+和3+被视为阳性。对所有IHC阳性患者以及阴性患者按2:1的比例进行荧光原位杂交(FISH)验证。
通过IHC确定的总体ALK突变率为6.2%,而FISH验证率为5.1%。FISH验证的ALK阳性率在匈牙利人为7.6%,塞尔维亚人为5.5%,斯洛伐克人为6.6%。肺腺癌的腺泡亚型与EML4-ALK阳性突变状态显著相关(p=0.02)。大多数患者为男性(56.9%),吸烟者(50.8%)或既往吸烟者(28.7%),患有腺泡型(55.4%)或实体型(35.9%)肺腺癌。IHC的敏感性和特异性分别为100%和98.9%。
通过IHC发现,接受手术治疗的肺腺癌患者的ALK突变率为6.2%,通过FISH为5.1%。肺腺癌的腺泡亚型与ALK阳性突变显著相关。