ROS1 rearrangements in lung adenocarcinoma: prognostic impact,therapeutic options and genetic variability

Background

While recent data show that crizotinib is highly effective in patients with ROS1 rearrangement, few data is available about the prognostic impact, the predictive value for different treatments, and the genetic heterogeneity of ROS1-positive patients.

Patients and Methods

1137 patients with adenocarcinoma of the lung were analyzed regarding their ROS1 status. In positive cases, next-generation sequencing (NGS) was performed. Clinical characteristics, treatments and outcome of these patients were assessed. Overall survival (OS) was compared with genetically defined subgroups of ROS1-negative patients.

Results

19 patients of 1035 evaluable (1.8%) had ROS1-rearrangement. The median OS has not been reached. Stage IV patients with ROS1-rearrangement had the best OS of all subgroups (36.7 months, p < 0.001). 9 of 14 (64.2%) patients had at least one response to chemotherapy. Estimated mean OS for patients receiving chemotherapy and crizotinib was 5.3 years. Ten patients with ROS1-rearrangement (52.6%) harbored additional aberrations.

Conclusion

ROS1-rearangement is not only a predictive marker for response to crizotinib, but also seems to be the one of the best prognostic molecular markers in NSCLC reported so far. In stage IV patients, response to chemotherapy was remarkable high and overall survival was significantly better compared to other subgroups including EGFR-mutated and ALK-fusion-positive NSCLC.     

非小细胞肺癌预后影响因素分析

目的:探讨非小细胞肺癌(NSCLC)患者的预后相关因素。方法:对2005年6月-2006年6月我院收治的162例非小细胞肺癌患者的临床、病理资料进行回顾性研究,采用Kaplan-Meier和COX回归方法分析评价各因素对预后的影响。结果:单因素分析表明KPS评分、手术与否、临床分期、治疗状况及治疗前血小板(PLT)、癌胚抗原(CEA)和神经元特异性烯醇化酶(NSE)的水平与NSCLC患者的预后有关。多因素分析表明,临床分期、治疗状况、血小板及血清癌胚抗原的水平是独立的预后影响因素。临床分期Ⅳ期、未治疗、PLT>300×109/L、CEA>5.0μg/L时,相对危险度(RR)分别为5.524、16.096、3.563、2.607。结论:治疗前血小板、血清CEA的水平、临床分期及治疗情况是NSCLC患者独立的预后影响因素。     

ALK融合基因阳性的晚期非小细胞肺癌靶向治疗进展

近十年来，晚期非小细胞肺癌（non-small cell lung cancer，NSCLC）在治疗方面出现重大的模式转变。关键致癌性突变（如驱动基因突变和染色体重排）的存在，使得靶向治疗相比传统的细胞毒性化学疗法显示出更高的敏感性。2007年间变性淋巴瘤激酶（anaplastic lymphoma kinase，ALK）基因与棘皮动物微管相关蛋白样-4（echinoderm microtubule-associated protein-4，EML4）基因融合突变首次在NSCLC患者中被发现。随后研究证实，ALK-EML4融合突变阳性的NSCLC（ALK+NSCLC）显示出对克唑替尼治疗的敏感性。随着后续一系列靶向治疗新药的研发，将ALK+NSCLC靶向治疗推向高潮。本综述回顾ALK+NSCLC的分子生物学发病机制、流行病学特征及检测方法，汇总其抑制剂的重要临床试验结果，并解读ALK+NSCLC抑制剂耐药机制及合并脑转移的最新研究进展。     

非小细胞肺癌新靶点ROS1融合基因

非小细胞肺癌(non-small cell lung cancer,NSCLC) 是造成人类死亡最多的恶性肿瘤之一,其五年生存率一直徘徊在20%以下。自肺癌领域首个分子靶向药物吉非替尼上市以来,靶向药物因其低毒、高效、便于给药的临床特点,己逐渐成为治疗NSCLC的重要选择之一。因此,筛选和证实肿瘤驱动基因已经成为未来靶向药物研发的重中之重。近来,越来越多的学者把焦点转移到ROS1融合基因上,并且已经有相关数据及研究表明ROS1融合基因被证实为NSCLC新的有潜力的治疗靶点,因此我们现就ROS1融合基因在NSCLC中的相关研究进展做一综述。     

Targeted therapies in non-small cell lung cancer: a focus on ALK/ROS1 tyrosine kinase inhibitors

Introduction: Anaplastic lymphoma kinase (ALK) and ROS1 rearrangements define important molecular subgroups of advanced non-small cell lung cancer (NSCLC). The identification of these genetic driver alterations created new potential for highly active therapeutic interventions. After discovery of ALK rearrangements in NSCLC, it was recognized that these confer sensitivity to ALK inhibition.

Areas covered: Crizotinib, the first-in-class ALK/ROS1/MET inhibitor, was initially approved as second-line treatment of ALK-positive advanced NSCLC but after this, it was firmly established as the standard first-line therapy for advanced ALK-positive NSCLC. After initial response to crizotinib, tumors inevitably relapse. Next-generation ALK inhibitors, more potent and brain-penetrable than crizotinib, may be effective in re-inducing remissions when cancers are still addicted to ALK. Ceritinib and alectinib are approved for metastatic ALK positive NSCLC patients, while brigatinib received granted accelerated approval by the United States Food and Drug Administration. Regarding ROS1 rearrangement, to date crizotinib is the only ALK-tyrosine kinase inhibitor receiving indication as treatment of ROS1 positive advanced NSCLC.

Expert commentary: Although novel ALK-inhibitors are under clinical investigation compared to crizotinib as front-line treatment for ALK-positive NSCLC, nowadays the current standard first-line therapy for these patients is crizotinib. Further research will clarify the best management of ALK-positive NSCLC, above all who progress on first-line crizotinib.     

ROS1阳性的非小细胞肺癌的检测及靶向治疗进展

ROS1融合基因是非小细胞肺癌（non-small cell lung cancer,NSCLC）靶向治疗的又一潜力靶点,随着相应靶向药物的使用,ROS1阳性的NSCLC患者生存期明显改善。越来越多针对ROS1融合基因的治疗药物面世,让这类患者有更多的选择。但持续性用药后的获得性耐药问题仍无法避免。本文就ROS1融合基因的检测方法、靶向治疗情况及耐药的机制和策略进行综述。     

The RET fusion gene and its correlation with demographic and clinicopathological features of non-small cell lung cancer: a meta-analysis

Purpose. The RET fusion gene is a novel oncogene observed in a subset of NSCLC in recent years. Nevertheless, the results of epidemiological studies concerning the gene remain unclear. Thus, a meta-analysis was conducted to evaluate the correlation of RET fusion gene with demographic and clinicopathological features of NSCLC. Methods. PubMed, Embase, and Web of Science databases were searched to identify eligible studies. The association of RET fusion gene occurrence with gender, age, smoking status, histology type and tumor stage were analyzed in meta-analysis. Subgroup analysis according to patients'' location (Asian and non-Asian) was also conducted. Odds ratio (OR) and 95% confidence interval (95% CI) were calculated to assess the correlation. Results. Nine studies with a total of 6,899 NSCLC patients met the inclusion criteria. A total of 84 patients with RET fusion gene were detected. The RET fusion gene was identified at significantly higher frequencies in female (OR = 0.55, 95%CI = 0.35–0.85) than male patients and in young (<60 ) patients (OR = 0.43, 95%CI = 0.19–0.99) than old patients (≤60 ), particularly in patients from Asian. A significant higher frequency was also identified in non-smokers (OR = 0.28, 95% CI = 0.16–0.49), and in patients with lung adenocarcinomas (OR = 3.59, 95%CI = 1.50–8.56). Additionally, no association between RET fusion gene and the TNM stage of tumor was observed. Conclusion. RET fusion gene occurred predominantly in Asian females with younger age, in non-smokers, and in lung adenocarcinomas patients. This subset of NSCLC patients might be good candidates for personalized diagnostic and therapeutic approaches.     

非小细胞肺癌根治术后生存分析

目的 肿瘤的局部复发和远处转移是非小细胞肺癌(non-small cell lung cancer,NSCLC)治疗失败和死亡的最主要原因.本研究评价与NSCLC患者复发/转移后生存时间(postrecurrence survival,PRS)和总生存率(overall survival,OS)相关的临床病理因素.方法 回顾性分析2005-01-01-2011-12-31于中日友好医院胸外科行肺叶切除+纵隔淋巴结清除的160例NSCLC患者临床资料及随访资料,病理分期为p I A～ⅢA期且经过随访均发生局部复发或者远处转移,应用SPSS 20.0对资料进行统计分析.应用Kaplan-Meier曲线及Cox回归对根治性切除术后OS和PRS相关风险因素进行分析.结果 160例患者平均年龄62岁,其中鳞癌41例,腺癌101例,其他类型NSCLC 18例(腺鳞癌11例,大细胞癌7例).随访终点43例发生局部复发,93例发生远处转移,24例同时发生局部复发和远处转.入组患者中位生存时间45个月;复发/转移后中位生存时间20个月.单因素分析结果显示,性别、TNM分期和复发/转移与OS有相关性,P＜0.05;年龄、吸烟指数、吸烟史、病理类型、淋巴血管浸润、复发/转移时间≤12个月、复发转移时间≤24个月、术后有无(放)化疗以及复发后有无治疗亦与OS具有相关性,P＜0.01.多因素分析结果显示,年龄(HR=0.23,95％CI:0.14～0.38,P＜0.01)、吸烟指数(HR=11.28,95％CI:2.53～50.26,P＜0.01)、TNM分期(HR=1.50,95％CI:1.08～2.07,P＜0.05)、复发时间≤24个月(HR=0.31,95％CI:0.16～0.60,P＜0.01)、术后有无放化疗(HR=0.82,95％CI:0.68～0.99,P＜0.05)、复发后有无治疗(HR=1.40,95％CI:1.24～1.58,P＜0.01)为影响OS的独立危险因素.单因素分析结果显示,年龄、吸烟指数、病理类型、TNM分期、术后有无(放)化疗和复发后有无治疗与PRS有相关性,P＜0.01;复发/转移亦与PRS有相关性,P＜0.05.多因素分析结果显示,年龄(HR=0.26,95％CI:0.18～0.45,P＜0.01)、吸烟指数(HR=1.73,95％CI:1.12～2.68,P＜0.05)、术后有无(放)化疗(HR=0.77,95％CI:0.66～0.91,P＜0.01)、复发后有无治疗(HR=1.36,95％CI:1.22～1.52,P＜0.01)为影响PRS的独立危险因素.结论 NSCLC患者OS和PRS与多个因素密切相关,其中术后早期(≤24个月)发生复发/转移的患者预后较差;复发/转移后治疗可以显著改善患者的OS与PRS.     

ALK and ROS1 testing on lung cancer cytologic samples: Perspectives

Cytologic sampling is the mainstay of diagnosing advanced lung cancer. Moreover, to select patients for personalized first‐line or second‐line treatment, epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) and c‐ros oncogene 1 (ROS1) rearrangements are tested on cytologic preparations. Commercially available fluorescence in situ hybridization (FISH) and immunocytochemistry (ICC) assays have primarily been used for the identification of cells harboring ALK or ROS1 gene fusions on histologic rather than cytologic preparations. However, it is now recognized that FISH and ICC also can be applied on cytologic samples provided the cytopathologist is aware that FISH and ICC results are not always concordant and that the performance of ICC largely depends on antibody clones, signal detection systems, and scoring systems. Notably, the routine clinical use of FISH and ICC may be replaced by emerging next‐generation sequencing and digital, color‐coded barcode technologies, which have the advantage of simultaneously evaluating ALK, ROS1, and EGFR alterations in a single analysis. Although their use in clinical cytologic practice remains to be fully established, it is conceivable that this technology will replace both FISH and ICC analyses in future diagnostic algorithms. Here, the authors review studies devoted to testing ALK and ROS1 on cytology specimens in an attempt to provide an update for the cytopathologist regarding current and evolving practice. Cancer Cytopathol 2017;125:817–30 . © 2017 American Cancer Society.     

Yes-associated protein 1 mediates initial cell survival during lorlatinib treatment through AKT signaling in ROS1-rearranged lung cancer

Tyrosine kinase inhibitors (TKIs) that target the ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) gene have shown dramatic therapeutic effects in patients with ROS1-rearranged non-small-cell lung cancer (NSCLC). Nevertheless, advanced ROS1-rearranged NSCLC is rarely cured as a portion of the tumor cells can survive the initial stages of ROS1-TKI treatment, even after maximum tumor shrinkage. Therefore, understanding the mechanisms underlying initial cell survival during ROS1-TKI treatment is necessary to prevent cell survival and achieve a cure for ROS1-rearranged NSCLC. In this study, we clarified the initial survival mechanisms during treatment with lorlatinib, a ROS1 TKI. First, we established a patient-derived ezrin gene-ROS1-rearranged NSCLC cell line (KTOR71). Then, following proteomic analysis, we focused on yes-associated protein 1 (YAP1), which is a major mediator of the Hippo pathway, as a candidate factor involved in cell survival during early lorlatinib treatment. Yes-associated protein 1 was activated by short-term lorlatinib treatment both in vitro and in vivo. Genetic inhibition of YAP1 using siRNA, or pharmacological inhibition of YAP1 function by the YAP1-inhibitor verteporfin, enhanced the sensitivity of KTOR71 cells to lorlatinib. In addition, the prosurvival effect of YAP1 was exerted through the reactivation of AKT. Finally, combined therapy with verteporfin and lorlatinib was found to achieve significantly sustained tumor remission compared with lorlatinib monotherapy in vivo. These results suggest that YAP1 could mediate initial cell resistance to lorlatinib in KTOR71 cells. Thus, combined therapy targeting both YAP1 and ROS1 could potentially improve the outcome of ROS1-rearranged NSCLC.     

246例非小细胞肺癌的预后影响因素分析

目的:分析246例非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的预后影响因素.方法:回顾性分析2010年1月至2014年12月246例非小细胞肺癌患者临床资料,采用Kaplan-Meier法进行生存分析,Log-rank检验和Cox模型预后影响因素行单因素和多因素分析.结果:全组患者中位生存时间为37.44个月.1年、3年、5年总生存率分别为72％、46％、26％.单因素分析显示,男性、年龄＞75岁、晚期、有吸烟史、有肝转移、无手术史非小细胞肺癌患者的中位生存期明显缩短(P＜0.05或P＜0.01).多因素分析显示,性别、疾病分期、是否吸烟和是否手术是影响非小细胞肺癌预后的独立因素(P ＜0.05或P＜0.01).结论:性别、疾病分期、是否吸烟和是否手术是非小细胞肺癌的独立预后因素.     

PFTK1在人非小细胞肺癌中的表达及临床意义

目的:研究PFTAIRE蛋白激酶1(PFTK1)在人类非小细胞肺癌(NSCLC)组织中的表达及其与NSCLC临床病理特征之间的关系,揭示PFTK1的表达在NSCLC中的临床意义。方法:采用免疫组织化学方法检测119例NSCLC组织中PFTK1的表达情况,并用χ²检验比较样本率,Kaplan-Meier法计算生存率,Log-Rank检验进行生存率的比较。结果:PFTK1在NSCLC组织中呈胞核和胞浆阳性。与癌旁组织比较,在119例NSCLC组织中,有76例肺癌组织PFTK1表达水平升高,占63.9%(76/119)。PFTK1的表达在NSCLC不同T分期间以及是否存在淋巴结转移组间的差异均具有统计学意义(P均<0.05),与年龄、性别、临床分期、病理分级、病理类型、肿瘤大小以及区域淋巴结N分期无明显相关性(P>0.05)。在肺鳞癌患者中控制分层因素N分期后进行生存分析显示PFTK1的表达水平越高,患者生存时间越短(P<0.05)。结论:PFTK1在人NSCLC中表达水平升高,并且PFTK1的表达与NSCLC的T分期及淋巴结转移具有相关性,影响NSCLC患者预后。PFTK1有望成为NSCLC潜在的生物学标志。     

小细胞肺癌与非小细胞肺癌的CT特征对比研究

目的:比较小细胞肺癌与非小细胞癌的CT表现,探讨小细胞肺癌的CT特征.方法:140例患者经肺穿刺活检病理结果分为小细胞肺癌组(35例)与非小细胞肺癌组(105例),分析两组患者的CT特征.结果:两组CT表现特征对比,在病灶长径与支气管关系、有无毛刺、是否存在胸膜凹陷、是否累及纵隔大血管、是否存在远处转移、是否累及叶、段支气管方面差异有统计学意义(P＜0.01).结论:小细胞肺癌的CT表现特点为病灶与支气管长径多平行,周边光滑、毛刺少见,常累及叶支气管、甚至累及段支气管,胸膜凹陷少见,常累及纵隔大血管等.     

Syntenin在非小细胞肺癌中的表达及其与患者总生存期的关系

目的：检测Syntenin在非小细胞肺癌（NSCLC）组织中的蛋白表达水平并探讨其临床意义。方法：采用组织芯片和免疫组织化学染色法,检测Syntenin在147例NSCLC及相应癌旁组织中的表达水平,并分析Syntenin的表达与NSCLC患者临床病理指标及预后的关系。结果：Syntenin在NSCLC组织中的阳性表达率（49.7%）显著高于癌旁组织（4.1%）（P < 0.01）。Syntenin的表达与NSCLC的淋巴结转移、临床分期和病理类型显著相关（P值分别为0.039、0.038、0.024）,与患者的性别和年龄无显著相关（P > 0.05）。Kaplan-Meier分析表明,Syntenin的表达与NSCLC患者的总生存期显著相关（P=0.028）。结论：Syntenin在NSCLC组织中高表达,并且其高表达预示了患者的不良预后。     

Progression-free survival and one-year milestone survival as surrogates for overall survival in previously treated advanced non-small cell lung cancer

The advent of immunotherapy leads to greater availability of effective subsequent treatments and extended survival in previously treated advanced non-small cell lung cancer (NSCLC), complicating the evaluation of overall survival (OS) in second-line NSCLC trials. Here, we aimed to assess the surrogacy of progression-free survival (PFS) and milestone survival for OS in second-line NSCLC trials investigating chemotherapy, targeted therapy and immunotherapy, respectively. We systemically searched for active-controlled, second-line NSCLC trials. The milestone time point was set at one-year based on pre-analysis. A two-stage meta-analytic validation model was adopted to assess associations between surrogate endpoint (SE) and OS and associations between treatment effects on SE and OS. Treatment effects on SE and OS were expressed as PFS hazard ratios (HR_PFS), 1 yr-milestone ratio (Ratio_1y-SUR) and HR_OS. Subgroup analyses stratified by treatment types and trial publication years evaluated the surrogacy in different clinical contexts. The study included 50 trials with 22,804 patients. One-year survival strongly correlated with OS (R²[95% confidence interval]: one-year survival -median OS = 0.707 [0.704–0.708]; Ratio_1y-SUR-HR_OS = 0.829 [0.828–0.831]). No correlation was established between PFS and OS (median PFS-median OS = 0.100 [0.098–0.101]; HR_PFS-HR_OS = 0.064 [0.059–0.069]), except in immunotherapy subgroup (HR_PFS-HR_OS = 0.835 [0.791–0.918]). In subgroup analyses, surrogacy of one-year survival persisted in different clinical contexts, and the disassociation between PFS and OS persisted in recent trials. One-year milestone survival showed strong surrogacy for OS in second-line NSCLC trials. Although no association was identified between PFS and OS, the strong HR_PFS-HR_OS correlation in immunotherapy trials indicates the potential of PFS as a SE in NSCLC trials involving immunotherapies.     

PD-L1、MDM2在EGFR罕见突变NSCLC患者中的表达及其临床意义

目的:探讨PD-L1和MDM2在表皮生长因子受体（epidermal growth factor receptor,EGFR）罕见突变的非小细胞肺癌（non-small cell lung cancer,NSCLC）患者中的表达,分析其与临床病理特征及预后的关系,探寻EGFR罕见突变人群的预后预测因子及免疫治疗的应用前景。方法:收集并随访69例EGFR罕见突变的NSCLC患者完整的临床病理资料（最终随访到64例,失访率7.25%）,采用免疫组化法检测51例保存完整的EGFR罕见突变的NSCLC福尔马林固定石蜡包埋组织中PD-L1、MDM2的表达水平,同时选取9例癌旁组织和8例正常组织的蜡块切片作为对照组,分析其与患者临床病理特征和预后的关系。结果:64例EGFR罕见突变的NSCLC患者,突变类型包括单突变41例（64.06%）,复合突变（同时存在两种或两种以上的EGFR突变）23例（35.94%）。NLR中位数为2.63,PD-L1在EGFR罕见突变NSCLC癌组织的阳性表达率为29.41%,在癌旁组织及正常肺泡上皮细胞中阴性表达（P=0.039）。MDM2在癌组织、癌旁组织和正常组织中的阳性表达率分别为86.27%、33.33%、12.5%,差异有明显统计学意义（P=0.000）。I/II期患者PD-L1在肿瘤细胞中的表达高于III/IV期（P=0.013）,而III/IV期患者MDM2在肿瘤中的表达高于I/II期患者（P=0.001）。而年龄、性别、是否吸烟、NLR、突变类型、病理分级与EGFR罕见突变癌患者组织中PD-L1、MDM2的表达水平无统计学差异（P>0.05）。64例患者的mOS为22.31个月。年龄、性别、吸烟、EGFR突变类型、PD-L1、MDM2表达与预后无明显相关。NLR<2.63患者的mOS优于NLR≥2.63（46.16个月vs 12.58个月）的患者,差异具有显著统计学意义（χ2=9.72,P=0.002）。病理分级为1/2级患者mOS优于3级患者（41.46个月vs 15.97个月）,差异具有明显统计学意义（χ2=6.17,P=0.013）。I/II期患者mOS优于III/IV期患者（59.17个月vs 15.97个月）,差异具有明显统计学意义（χ2=18.89,P=0.000）。Cox多因素回归分析:NLR（HR=2.667,P=0.007）、分期（HR=8.778,P=0.000）是EGFR罕见突变NSCLC患者的独立预后因素。结论:NLR可考虑作为EGFR罕见突变NSCLC患者预后的疗效预测因子;PD-L1在EGFR罕见突变的NSCLC中阳性表达率较高,免疫治疗可能获益。     

EML4-ALK fusion gene in non-small cell lung cancer

Non-small cell lung cancer (NSCLC) is a malignant tumor with a high morbidity and mortality rate that is a threat to human health. With the development of molecular targeted research, breakthroughs have been made on the molecular mechanism of lung cancer. The echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion gene is one of the most important pathogenic driver genes of NSCLC discovered thus far. Four generations of targeted drugs for EML4-ALK have been developed, with patients benefiting significantly from these drugs. Therefore, EML4-ALK has become a research hotspot in NSCLC. The aim of the present study is to introduce the current research progress of EML4-ALK and its association with NSCLC.     

Disparate survival trends in histologic subtypes of metastatic non-small cell lung cancer: a population-based analysis

Erlotinib, bevacizumab, and pemetrexed improved survival of metastatic non-small cell lung cancer (mNSCLC) in clinical trials, but their benefits are restricted to non-squamous histology. We studied recent survival trends in mNSCLC subpopulations defined by histology and associated clinical factors correlating with adenocarcinoma or endothelial growth factor receptor mutations. Using the Surveillance, Epidemiology and End Results database, we calculated relative survival at 1 year from diagnosis for mNSCLC cases diagnosed in 2000-2011. Trends by histology, age, sex, race, prevalence of smoking or poverty, expressed as annual percent change (APC) using joinpoint regression, were compared by test of slope parallelism (P_par). Among 226,446 cases, 47% had adenocarcinoma, 20% squamous carcinoma, 6% other, and 27% unspecified histology. The proportion of cases designated as adenocarcinoma significantly increased after 2005. One-year survival increased from 23.5% in 2000 to 30.5% in 2010, significantly more for adenocarcinoma (APC, 3.3%) than squamous carcinoma (APC, 2.1%, P_par=0.0018). For patients with adenocarcinoma, these trends were significantly better for Asians than Whites (P_par=0.012) and for areas with fewer smokers (P_par=0.014). Such differences were not observed for squamous carcinoma (P_par=0.87 and 0.14, respectively). The absolute disparity in one-year survival between adenocarcinoma and squamous carcinoma increased from 1.6% in 2000 to 5.5% in 2010. The disparity between Asians and Whites increased from 5.2% to 13.1%, respectively. These data demonstrate that improvement in survival of mNSCLC since 2000 is now evident on a population scale. The superior increment for patients with adenocarcinoma, particularly among Asians and in communities with fewer smokers, suggests impact of the newly introduced, histology-specific agents, rather than better supportive care alone. Growing disparities between adenocarcinoma and squamous carcinoma highlight the needs to intensify research on treatment for subgroups that did not benefit from recent advances.     

非小细胞肺癌ALK基因重排检测

目的 通过荧光原位杂交(FISH)方法检测非小细胞肺癌(NSCLC)患者间变性淋巴瘤激酶(ALK)基因重排.方法 根据ALK断裂重排方式及特点,设计并制备红/绿双色荧光探针.以人外周血培养细胞为检测对象评价ALK融合基因检测探针的敏感性和特异性,以NSCLC石蜡组织样本为对象进行ALK基因重排检测以评价探针的性能.结果 本研究制备的荧光探针在EB病毒(EBV)转化的人淋巴细胞检测中的特异性和敏感性均可达到100％.在对2例NSCLC患者石蜡包埋组织样本检测中,检测阴性、阳性各1例,检测结果与免疫组织化学检测结果一致.结论 本研究中制备的双色荧光探针可用于NSCLC ALK基因重排的检测.