Clinical & Experimental Metastasis

, Volume 28, Issue 3, pp 271–282 | Cite as

Expression and significance of HER family receptors in neuroblastic tumors

  • Ewa Izycka-Swieszewska
  • Agnieszka Wozniak
  • Elzbieta Drozynska
  • Jacek Kot
  • Wieslawa Grajkowska
  • Teresa Klepacka
  • Danuta Perek
  • Sylwia Koltan
  • Ewa Bien
  • Janusz Limon
Research Paper


HER receptor family plays an important role in normal embryonic development and is involved in pathogenesis and progression of some types of cancer. Neuroblastic tumors (NT) are common pediatric neoplasms with a poor outcome in a significant number of patients. The biological and prognostic role of HER family in NT is not well established. In the current study we evaluated HER1–4 receptors expression, their prognostic significance and clinicopathological correlations in a series of 103 NTs by immunohistochemical assessment of HER1–4 expression and FISH analysis of EGFR and HER2 copy number status. HER receptors are commonly expressed in NT but it was not due to EGFR or HER2 amplification. EGFR, HER2 and HER4 show correlation with tumor histology. It seems that these receptors take part in neuroblastic cell differentiation and Schwannian stroma development. EGFR and HER2 positivity are more frequently found in favorable histological risk group of tumours (P = 0.004 and P = 0.01 respectively) while high expression of HER4 is significantly more often found in patients with metastatic disease (P = 0.03). Moreover tumors with HER2 polysomy were more often found in children ≤18 months, with localized disease, and favorable histological group. Our study showed that the role of HER family members in NT biology is interrelated and complex but their expression level may present a novel prognostic factor for NT patients outcome.


Neuroblastoma EGFR HER2 HER3 HER4 Prognostic factor FISH Immunophenotype 



This study was supported by a grant from Polish MEN N401 176 31/3867. The authors thank Dagmara Warzocha and Anita Matyskiel for their excellent technical support.

Conflict of interest



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Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Ewa Izycka-Swieszewska
    • 1
  • Agnieszka Wozniak
    • 2
    • 3
  • Elzbieta Drozynska
    • 4
  • Jacek Kot
    • 5
  • Wieslawa Grajkowska
    • 6
  • Teresa Klepacka
    • 7
  • Danuta Perek
    • 8
  • Sylwia Koltan
    • 9
  • Ewa Bien
    • 4
  • Janusz Limon
    • 2
  1. 1.Department of PathomorphologyMedical University of GdańskGdanskPoland
  2. 2.Department of Biology and GeneticsMedical University of GdańskGdanskPoland
  3. 3.Laboratory of Experimental Oncology, Department of General Medical OncologyCatholic University Leuven, University HospitalsLeuvenBelgium
  4. 4.Department of Pediatrics, Hematology, Oncology and EndocrinologyMedical University of GdańskGdanskPoland
  5. 5.Department of Hyperbaric Medicine and Sea RescueMedical University of GdańskGdyniaPoland
  6. 6.Department of PathologyChildren’s Health Memorial InstituteWarsawPoland
  7. 7.Department of PathologyInstitute of Mother and ChildWarsawPoland
  8. 8.Department of OncologyChildren’s Health Memorial InstituteWarsawPoland
  9. 9.Department of Pediatrics, Hematology and OncologyNicolaus Copernicus University Torun, Collegium Medicum University HospitalBydgoszczPoland

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