Brcic Luka, Jakopovic Marko, Misic Marija, Seiwerth Fran, Kern Izidor, Smojver-Jezek Silvana, Quehenberger Franz, Samarzija Miroslav, Seiwerth Sven
Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036, Graz, Austria.
Institute of Pathology, University of Zagreb School of Medicine, Zagreb, Croatia.
Diagn Pathol. 2016 Sep 21;11(1):90. doi: 10.1186/s13000-016-0544-9.
Many studies have been published on the mutational status of patients with lung adenocarcinomas, and great population-based variability in mutation frequencies has been reported. The main objective of the present study was to analyze the EGFR, KRAS and ALK mutation status in a representative cohort of patients in Croatia with lung adenocarcinomas and to correlate the mutational status with clinical data.
All patients who were newly diagnosed within 6 months with histologically proven primary lung adenocarcinomas were included. Mutational analyses for EGFR and KRAS mutations were performed in a cobas z 480 analyzer. ALK immunohistochemistry was performed using the D5F3 clone on Benchmark XT instrument. Clinical data were obtained from the medical records.
Of the 324 patients, 59.9 % were male. At the time of diagnosis, the patients ranged in age range from 35 to 88 years (median 63 years). Most of the patients were current smokers or former smokers (77.2 %). EGFR mutations were found in 15.7 % of the patients, and of these mutations, exon 19 deletion was the most common (45.1 %). KRAS mutations were present in 34.9 % of the patients, while 4.1 % of patients were ALK-positive. The statistical significance of the presence of mutations was detected for both gender and smoking.
The detected mutation rates demonstrated a slightly higher prevalence of KRAS mutations, but not a higher prevalence of EGFR mutations or ALK gene rearrangement, in comparison with the rates found in other European countries. EGFR and ALK mutational status showed a statistically significant correlation with gender as well as with smoking, while KRAS mutation status showed a statistically significant correlation only with smoking.
关于肺腺癌患者的突变状态已发表了许多研究,并且报道了基于人群的突变频率存在很大差异。本研究的主要目的是分析克罗地亚具有代表性的肺腺癌患者队列中的表皮生长因子受体(EGFR)、 Kirsten大鼠肉瘤病毒癌基因(KRAS)和间变性淋巴瘤激酶(ALK)突变状态,并将突变状态与临床数据相关联。
纳入所有在6个月内新诊断为组织学证实的原发性肺腺癌的患者。在cobas z 480分析仪中进行EGFR和KRAS突变的突变分析。使用D5F3克隆在Benchmark XT仪器上进行ALK免疫组织化学检测。临床数据从病历中获取。
324例患者中,59.9%为男性。诊断时,患者年龄在35至88岁之间(中位数为63岁)。大多数患者为当前吸烟者或既往吸烟者(77.2%)。15.7%的患者发现EGFR突变,其中外显子19缺失是最常见的(45.1%)。34.9%的患者存在KRAS突变,而4.1%的患者ALK呈阳性。在性别和吸烟方面均检测到突变存在的统计学意义。
与其他欧洲国家发现的比率相比,检测到的突变率显示KRAS突变的患病率略高,但EGFR突变或ALK基因重排的患病率并未更高。EGFR和ALK突变状态与性别以及吸烟均显示出统计学显著相关性,而KRAS突变状态仅与吸烟显示出统计学显著相关性。