期刊文献+

525例肺癌中ALK阳性病例临床病理特征研究及检测方法探讨 被引量:18

The Research of Clinical Pathological Features of ALK Positive Lung Cancer in 525 Patients and the Discussion of Detection Methods
下载PDF
导出
摘要 背景与目的间变性淋巴瘤激酶(anaplastic lymphoma kinase,ALK)融合基因的产生对肺癌的发生、发展起重要作用。ALK酪氨酸激酶抑制剂(tyrosine kinase inhibitors,TKIs)对ALK阳性肺癌患者具有较好的疗效。提高ALK阳性病例的检出率对患者有重要意义。本研究旨在探讨ALK阳性病例的临床病理特征、免疫组化(immunohistochemistry,IHC)方法在筛查ALK阳性病例中的意义,以及荧光原位杂交(fluorescence in situ hybridization,FISH)在检测流程中的作用。方法应用IHC方法检测525例肺癌患者组织标本中ALK的表达,并对其中34例进行FISH验证。结果肺癌病例中ALK IHC阳性率为5.14%(27/525)。ALK阳性组中年轻患者、女性患者比例高于ALK阴性组(P<0.05);实体型肺腺癌在ALK阳性组中比例明显增高,而腺泡型与贴壁型比例明显降低,与阴性组相比有差异(P<0.05)。34例病例进行FISH验证,IHC与FISH符合率随IHC阳性程度的增加递增。伴或不伴有EGFR突变的ALK IHC阳性病例,都必须进行ALK FISH验证。结论 IHC可以作为可靠的ALK筛查手段,提高ALK的检出率。FISH检测对确诊ALK阳性肺癌具有重要意义。 Background and objective The fusion (rearrangement) ofanaplasticlymphomakinase (ALK)genehas been identified as an import factor to the tumorigenesis and development of lung cancer. ALK tyrosine kinase inhibitors (ALKTKIs) have been proved to have good effects to ALK positive lung cancers, 1he increasement of the relevance ratio of ALK will be very important to patients. The aim of this study is to investigate the clinical pathological features of ALK positive lung cancer, and the roles ofimmunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in screening and confirming the ALK positive cases in the testing flow of ALK. Methods IHC analysis of ALK in tumor specimens was performed on 525 lung cancer patients. 34 cases among them were confirmed by FISH. Results The positive incidence of ALK by IHC was 5.14% (27/525). The ALK positive patients were significantly younger than ALK negative patients (P〈O.05), and femal was predominant (P〈0.05). The proportion of solid predominant adenocarcinoma was significantly higher in ALK positive patients (P〈0.05). While acinar and lepidic predominant adenocarcinoma were significantly lower in ALK positive patients (P〈0.05). FISH was applied in 34 cases. The coincidence rate was increased with the increasement of positive intensity of IHC staining. All the IHC positive cases with or without EGFR mutation must be confirmed by FISH. Conclusion IHC is a reliable detection method to screening the ALK in lung cancer, and then enhance the relevance ration. To make a definite diagnosis of ALK positive lung cancer, FISH is a significant detection method.
出处 《中国肺癌杂志》 CAS 北大核心 2014年第3期226-232,共7页 Chinese Journal of Lung Cancer
关键词 肺肿瘤 ALK EGFR 免疫组化 FISH Lung neoplasms Anaplastic lymphoma kinase gene (ALK) Epidermal growth factor receptor (EGFR) Immunohistochemistry (IHC) Fluorescence in situ hybridization (FISH)
  • 相关文献

参考文献20

  • 1Siegel R, Ward E, Brawley O, et al. Cancer statistics, 2011, the impact of eliminating socioeconomic and racial Disparities on premature cancer deaths. CA CancerJ Clin, 2011, 61 (4): 212-236.
  • 2Soda M, Choi YL, Enomoto M, et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature, 2007, 488(7153): 561-566.
  • 3Soda M, Takada S, Takeuchi K, et aI. A mouse model for EML4-ALK-positive lung cancer. Proc Nail Acad Sci, 2008, 105(50): 19893-19897.
  • 4Seto T, Kiura K, Nishio M, et al. CH5424802 (RO5424802) for patients with ALK-rearranged advanced non-small-cell lung cancer (AF-0011P study): a single-arm, open-label, phase 1-2 study. Lancet Oncol, 2013, 14(7): 590-598.
  • 5Katayama R, Khan TM, Benes C, et al. Therapeutic strategies to overcome crizotinib resistance in non-small cell lung cancers harboring the fusion oncogene EML4-ALK. Proc Nail Acad Sci USA, 2011,108 (18 ): 7535-7540.
  • 6张绪超,陆舜,张力,王长利,程颖,李甘地,Tony Mok,Mok,黄诚,刘晓晴,王洁,王孟昭,张沂平,周建英,周晓燕,林冬梅,杨衿记,李慧,陈海泉,钟文昭,吴一龙.中国间变性淋巴瘤激酶(ALK)阳性非小细胞肺癌诊断专家共识(2013版)[J].中华病理学杂志,2013,42(6):402-406. 被引量:94
  • 7Gainor JE Varghese AM, Ou SH, et al. ALK rearrangements are mutually exclusive with mutations in EGFR or KRAS: an analysis of 1,683 patients with non-small cell lung cancer. Clin Cancer Res, 2013, 19(15): 4273-4281.
  • 8Yang JJ, Zhang XC, Su J, et al. Lung cancers with concomitant EGFR mutations and ALK rearrangements: diverse responses to EGFR-TKI and crizotinib in relation to diverse receptors phosphorylation. Clin Cancer Res, 2014. [Epub ahead of print].
  • 9曾珠,吴一龙.EML4-ALK与EGFR基因突变共存型非小细胞肺癌研究进展[J].中国肺癌杂志,2011,14(11):880-884. 被引量:25
  • 10Beasley MB, Brambilla E, Travis WD, et al. The 2004 World Health Organization classification of lung tumors. Semin Roentgenol, 2005, 40(2): 90-97.

二级参考文献58

  • 1Matsumura I, Mizuki M, Kanakura Y. Roles for deregulated receptor tyrosine kinases and their downstream signaling molecules in hematologic malignancies. Cancer Sci, 2008, 99(3): 479-485.
  • 2Yang JJ, Zhang XC, Jiang BY, et al. Research prog- ress of individual therapy of advanced NSCLC targeting EML4-ALK fusion gene. Oncology Prog- ress, 2010, 8(6): 538-545.
  • 3Sordella R, Bell DW, Haber DA, et al. Gefitinibsensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways. Science, 2004, 305(5687): 1163-1167.
  • 4Kosaka T, Yatabe Y, Endoh H, et al. Mutations of the epidermal growth factor receptor gene in lung cancer: biological and clinical implications. Cancer Kes, 2004, 64(24): 8919-8923.
  • 5Shigematsu H, Lin L, Takahashi T, et al. Clinical and biological features asso- ciated with epidermal growth factor receptor gene mutations in lung cancers. J Natl Cancer Inst, 2005, 97(5): 339-346.
  • 6Pao W, Wang TY, Riely GJ, et al. KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. PLoS Med, 2005, 2(1): el7.
  • 7Wu JY, Wu SG, Yang CH, et al. Lung cancer with epidermal growth factor receptor exon 20 mutations is associated with poor gefitinib treatment response. Clin Cancer Res, 2008, 14(15): 4877-4882.
  • 8Keedy VL, Temin S, Somerfield MR, et al. American society of clinical oncol- ogy provisional clinical opinion: epidermal growth factor receptor (EGFR) mutation testing for patients with advanced non-small-cell lung cancer considering first-line EGFR tyrosine kinase inhibitor therapy. J Clin Oncol, 2011, 29(15): 2121-2127.
  • 9Wu YL, Zhong WZ, Li LY, et al. Epidermal growth factor receptor mutations and their correlation with gefitinib therapy in patients with non-small cell lung cancer: a meta-analysis based on updated individual patient data from six medical centers in China's Mainland.J qqaorac Oncol, 2007, 2(5): 430-439.
  • 10Camidge DR, Bang Y, Kwak EL, et al. Progression-free survival (PFS) from a phase I study of crizotinib (PF-02341066) in patients with ALK-positive non-small cell lung cancer (NSCLC). J Clin Oncol, 2011, (suppl): abstr 2501.

共引文献115

同被引文献157

  • 1彭红,韩宝惠,李小青,陶路宁.1279例肺癌患者临床特征及生存率分析[J].中国癌症杂志,2011,21(5):354-358. 被引量:54
  • 2Letícia Trivellato Gresta,Ismael Alves Rodrigues-Júnior,Lúcia Porto Fonseca de Castro,Geovanni Dantas Cassali,Mnica Maria Demas lva-res Cabral.Assessment of vascular invasion in gastric cancer: A comparative study[J].World Journal of Gastroenterology,2013,19(24):3761-3769. 被引量:11
  • 3王孟昭,陈勇,钟巍,张力,徐凌,施举红,钟旭,肖毅,蔡柏蔷,李龙芸.经支气管镜淋巴结针吸活检对肺癌的诊断意义[J].中华肿瘤杂志,2006,28(7):533-535. 被引量:35
  • 4董强刚,韩宝惠,黄进肃,杨立民,黄建,赵春英,卢丽琴.176例非小细胞肺癌的EGFR基因突变分析[J].中华肿瘤杂志,2006,28(9):686-690. 被引量:53
  • 5Takeuchi K, Choi YL, Soda M, et al. Multiplex reverse transcription-PCR screening for EMIA-ALK fusion transcripts [ J ]. Clin Cancer Res, 2008, 14(20) :6618-6624.
  • 6Soda M, Choi YL, Enomoto M, et al. Identification of the transforming EMIA-ALK fusion gene in non-small-cell lung cancer [J]. Nature, 2007, 448(7153) :561-566.
  • 7Bergethon K, Shaw AT, Ou SH, et al. ROS1 rearrangements define a unique molecular class of lung cancers[ J]. J Clin Oncol, 2012,30 ( 8 ) : 863-870.
  • 8Takeuehi K, Choi YL, Togashi Y, et al. KIF5B-ALK, a novel fusion oncokinase identified by an immunohistochemistry-based diagnostic system for ALK-positive lung cancer [ J ]. Clin Cancer Res.2009.15 (9).3143-3149.
  • 9Rikova K, Guo A, Zeng Q, et al. Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer [ J ]. Cell, 2007, 131(6) :1190-1203.
  • 10Cai W, Li X, Su C, et al. ROS1 fusions in Chinese patients with non-small-cell lung cancer [ J ]. Ann Oncol, 2013,24 ( 7 ) : 1822- 1827.

引证文献18

二级引证文献106

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部