Concomitant EGFR mutation and ALK rearrangement in lung adenocarcinoma is more frequent than expected: Report of a case and review of the literature with demonstration of genes alteration into the same tumor cells

被引:58
作者
Baldi, Licia [1 ]
Mengoli, Maria Cecilia [2 ]
Bisagni, Alessandra [3 ]
Banzi, Maria Chiara [1 ]
Boni, Corrado [1 ]
Rossi, Giulio [2 ]
机构
[1] Azienda Arcispedale S Maria Nuova IRCCS, Unit Oncol, Dept Oncol & Adv Technol, I-42123 Reggio Emilia, Italy
[2] Azienda Osped Univ Policlin, Unit Pathol, Modena, Italy
[3] Azienda Arcispedale S Maria Nuova IRCCS, Unit Pathol, Dept Oncol & Adv Technol, I-42123 Reggio Emilia, Italy
关键词
Lung; Adenocarcinoma; EGFR; ALK; FISH; Immunohistochemistry; NSCLC; GROWTH-FACTOR-RECEPTOR; EML4-ALK FUSION GENE; TYROSINE KINASE; CANCER; KRAS; CRIZOTINIB; RESISTANCE; TRANSLOCATION; INHIBITORS; GEFITINIB;
D O I
10.1016/j.lungcan.2014.09.011
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Oncogenic drivers in lung non-small-cell lung cancer (NSCLC) are considered mutually exclusive, but a review of the literature reveals that concomitant EGFR mutations and ALK rearrangement may occur in a subset of NSCLC. We report here a case of pulmonary adenocarcinoma with concomitant EGFR mutation in exon 21 (L858R) and ALK rearrangement in naive and relapsed tumors. Tumor cells seem to harbor both gene alterations and the patient had a long-lasting response both to EGFR inhibitor in second line and ALK inhibitor once tumor progressed. A speculative discussion on molecular mechanisms underlying this uncommon phenomenon and practical points about epidemiologic, clinicopathologic features and therapeutic options in this intriguing subset of double-positive tumor are reported. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:291 / 295
页数:5
相关论文
共 21 条
  • [1] Parallel FISH and Immunohistochemical Studies of ALK Status in 3244 Non-Small-Cell Lung Cancers Reveal Major Discordances
    Cabillic, Florian
    Gros, Audrey
    Dugay, Frederic
    Begueret, Hugues
    Mesturoux, Laura
    Chiforeanu, Dan Cristian
    Dufrenot, Leila
    Jauffret, Vincent
    Dachary, Dominique
    Corre, Romain
    Lespagnol, Alexandra
    Soler, Gwendoline
    Dagher, Julien
    Catros, Veronique
    Le Calve, Michele
    Merlio, Jean-Philippe
    Belaud-Rotureau, Marc-Antoine
    [J]. JOURNAL OF THORACIC ONCOLOGY, 2014, 9 (03) : 295 - 306
  • [2] A case of lung adenocarcinoma harboring exon 19 EGFR deletion and EML4-ALK fusion gene
    Chen, Xiaoxia
    Zhang, Jie
    Hu, Qiong
    Li, Xuefei
    Zhou, Caicun
    [J]. LUNG CANCER, 2013, 81 (02) : 308 - 310
  • [3] Long-Term Response to Gefitinib and Crizotinib in Lung Adenocarcinoma Harboring Both Epidermal Growth Factor Receptor Mutation and EML4-ALK Fusion Gene
    Chiari, Rita
    Duranti, Simona
    Ludovini, Vienna
    Bellezza, Guido
    Pireddu, Anjuta
    Minotti, Vincenzo
    Bennati, Chiara
    Crino, Lucio
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2014, 32 (09) : E30 - E32
  • [4] ALK Rearrangements Are Mutually Exclusive with Mutations in EGFR or KRAS: An Analysis of 1,683 Patients with Non-Small Cell Lung Cancer
    Gainor, Justin F.
    Varghese, Anna M.
    Ou, Sai-Hong Ignatius
    Kabraji, Sheheryar
    Awad, Mark M.
    Katayama, Ryohei
    Pawlak, Amanda
    Mino-Kenudson, Mari
    Yeap, Beow Y.
    Riely, Gregory J.
    Iafrate, A. John
    Arcila, Maria E.
    Ladanyi, Marc
    Engelman, Jeffrey A.
    Dias-Santagata, Dora
    Shaw, Alice T.
    [J]. CLINICAL CANCER RESEARCH, 2013, 19 (15) : 4273 - 4281
  • [5] Jürgens J, 2014, FUTURE ONCOL, V10, P529, DOI [10.2217/fon.13.194, 10.2217/FON.13.194]
  • [6] Kim TJ, 2014, J SURG ONCOL
  • [7] EML4-ALK fusion gene and efficacy of an ALK kinase inhibitor in lung cancer
    Koivunen, Jussi P.
    Mermel, Craig
    Zejnullahu, Kreshnik
    Murphy, Carly
    Lifshits, Eugene
    Holmes, Alison J.
    Choi, Hwan Geun
    Kim, Jhingook
    Chiang, Derek
    Thomas, Roman
    Lee, Jinseon
    Richards, William G.
    Sugarbaker, David J.
    Ducko, Christopher
    Lindeman, Neal
    Marcoux, J. Paul
    Engelman, Jeffrey A.
    Gray, Nathanael S.
    Lee, Charles
    Meyerson, Matthew
    Janne, Pasi A.
    [J]. CLINICAL CANCER RESEARCH, 2008, 14 (13) : 4275 - 4283
  • [8] Good Response to Gefitinib in Lung Adenocarcinoma Harboring Coexisting EML4-ALK Fusion Gene and EGFR Mutation
    Kuo, Yao-Wen
    Wu, Shang-Gin
    Ho, Chao-Chi
    Shih, Jin-Yuan
    [J]. JOURNAL OF THORACIC ONCOLOGY, 2010, 5 (12) : 2039 - 2040
  • [9] Lindeman NI, 2013, ARCH PATHOL LAB MED, V137, P828, DOI [10.5858/arpa.2012-0720-OA, 10.1097/JTO.0b013e318290868f]
  • [10] Molecular Pathways: Resistance to Kinase Inhibitors and Implications for Therapeutic Strategies
    Lovly, Christine M.
    Shaw, Alice T.
    [J]. CLINICAL CANCER RESEARCH, 2014, 20 (09) : 2249 - 2256