Pathology & Oncology Research

, Volume 25, Issue 1, pp 217–224 | Cite as

The Presence of ALK Alterations and Clinical Relevance of Crizotinib Treatment in Pediatric Solid Tumors

  • Luca Felkai
  • Rita Bánusz
  • Ilona Kovalszky
  • Zoltán Sápi
  • Miklós Garami
  • Gergő Papp
  • Katalin Karászi
  • Edit Varga
  • Monika CsókaEmail author
Original Article


Soft tissue sarcomas (STS) and neuroblastomas (NBL), are childhood malignancies still associated with poor prognoses despite the overall improvement in childhood tumor survival of the past decades. Anaplastic lymphoma kinase (ALK) inhibition is promising new strategy to improve the outcome of these pediatric tumors. Eighteen histologic samples of pediatric STS and 19 NBL patients were analyzed for ALK abnormalities using fluorescent in situ hybridization (FISH) with break-apart probes and immunohistochemistry (IHC). ALK alterations were presented in 20 of the 37 sections. The presence of ALK alteration in NBL samples were detected using IHC in 84,2% of all cases compared to 21,1% FISH positivity. In STS cases the results were less different (IHC 16,7% vs FISH 22,2%). The difference can be explained by the different type of molecular alterations. FISH method detected translocation and amplification, but not the point mutation of ALK gene. IHC confirmed the diagnosis by detecting the expression of ALK protein.After ALK positivity was proven, the effectiveness and safety of the crizotinib therapy was examined in 4 patients (1 alveolar rhabdomyosarcoma (RMA), 1 embryonal rhabdomyosarcoma (RME), 1 inflammatory myofibroblastic tumor (IMT), 1 NBL). We observed continuous remission of the IMT patient, all other cases the inhibitor treatment was not curative.Our findings underline the importance of screening the ALK status parallel with both IHC and FISH. Crizotinib treatment had a long-term effect in ALK positive IMT patients, however itwas only temporary efficient in relapsed, progressive STS and NBL.


ALK Crizotinib Soft tissue sarcoma Neuroblastoma Inflammatory myofibroblastic tumor 

List of Abbreviations


akt murine thymoma viral oncogene


anaplasticlarge cell lymphoma


anaplastic lymphoma kinase


alveolarsoft part sarcoma


Cooperative Weichteilsarkom Studiengruppe


c mesenchymal epithelial transition growth factor




diffuselarge B-cell lymphoma


diffusion-weighted whole-body imaging with background body signal suppression


Food and Drug Administration


fluorescent in situ hybridization


high risk




inflammatory myofibroblastic tumor




mammalian target of rapamiycin




non-small cell lung carcinoma


phosphatidylinozitol 3-kinase




alveolar rhabdomyosarcoma


embryonal rhabdomyosarcoma


receptor originated from nantes


ROS protooncogene


real-time polymerase chain reaction


International Society of Pediatric Oncology Europe Neuroblastoma


saline sodium citrate


signal transducer and activator of transcription


soft tissue sarcoma



We thank both the coworkers of the soft tissue tumor and the molecular pathology research group, especially Zoltánné Polgár, Linda Gyurcsó-Deák and Anna Tamási for the help with the immunohistochemistry and FISH investigation. For lecturing the publication, we thank Dóra Török MD PhD.

Compliance with Ethical Standards

Ethics Approval and Consent to Participate

Investigations were approved by the Institutional Ethical Review Board. / The study protocol was approved by the Ethics and Scientific committee of the participating institution. TUKEB 7/2006.

Consent for Publication and Competing Interests

All of the authors declare that they have no competing interests. All authors have read and approved the final manuscript.


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Copyright information

© Arányi Lajos Foundation 2017

Authors and Affiliations

  • Luca Felkai
    • 1
  • Rita Bánusz
    • 1
  • Ilona Kovalszky
    • 2
  • Zoltán Sápi
    • 2
  • Miklós Garami
    • 1
  • Gergő Papp
    • 2
  • Katalin Karászi
    • 2
  • Edit Varga
    • 1
  • Monika Csóka
    • 1
    Email author
  1. 1.2nd Department of PediatricsSemmelweis UniversityBudapestHungary
  2. 2.1st Department of Pathology and Experimental Cancer ResearchSemmelweis UniversityBudapestHungary

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