title: Expression and significance of HER family receptors in neuroblastic tumors.
abstract: 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.
authors.affiliation: Department of Pathomorphology, Medical University of Gdańsk, ul Dębinki 7, 80-211 Gdansk, Poland. eczis@wp.pl
authors.forename: Ewa
authors.initials: E
authors.lastname: Izycka-Swieszewska
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Wozniak
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Drozynska
authors.forename: Jacek
authors.initials: J
authors.lastname: Kot
authors.forename: Wieslawa
authors.initials: W
authors.lastname: Grajkowska
authors.forename: Teresa
authors.initials: T
authors.lastname: Klepacka
authors.forename: Danuta
authors.initials: D
authors.lastname: Perek
authors.forename: Sylwia
authors.initials: S
authors.lastname: Koltan
authors.forename: Ewa
authors.initials: E
authors.lastname: Bien
authors.forename: Janusz
authors.initials: J
authors.lastname: Limon
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D007231:Infant, Newborn; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D020893:Receptor, ErbB-3 / Q000235:genetics / Q000378:metabolism*; D066247:Receptor, ErbB-4
chemical_list: D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D066247:Receptor, ErbB-4; C587689:ERBB4 protein, human