Expression and localization of serine protease Htra1 in neuroblastoma: correlation with cellular differentiation grade

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• 作者：Velia D’Angelo (1)
  Giulia Pecoraro (1)
  Paolo Indolfi (1)
  Adriana Iannotta (1)
  Vittoria Donofrio (2)
  Maria Elena Errico (2)
  Cristiana Indolfi (1)
  Maria Ramaglia (1)
  Angela Lombardi (3)
  Martina Di Martino (1)
  Vincenzo Gigantino (4)
  Alfonso Baldi (3)
  Michele Caraglia (3)
  Antonio De Luca (5)
  Fiorina Casale (1)
  
• 关键词：HtrA1 ; Serine protease ; Neuroblastoma ; Ganglioneuroblastoma ; Tumour grading
• 刊名：Journal of Neuro-Oncology
• 出版年：2014
• 出版时间：April 2014
• 年：2014
• 卷：117
• 期：2
• 页码：287-294
• 全文大小：915 KB
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• 作者单位：Velia D’Angelo (1)
  Giulia Pecoraro (1)
  Paolo Indolfi (1)
  Adriana Iannotta (1)
  Vittoria Donofrio (2)
  Maria Elena Errico (2)
  Cristiana Indolfi (1)
  Maria Ramaglia (1)
  Angela Lombardi (3)
  Martina Di Martino (1)
  Vincenzo Gigantino (4)
  Alfonso Baldi (3)
  Michele Caraglia (3)
  Antonio De Luca (5)
  Fiorina Casale (1)
  
  1. Pediatric Oncology Service, Pediatric Department, Second University of Naples, Naples, Italy
  2. Pediatric Pathology Unit, Pausilipon Hospital, Naples, Italy
  3. Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy
  4. Pathology Unit, National Institute of Tumours “Fondazione G. Pascale- Naples, Italy
  5. Department of Medicine and Public Health, Section of Clinical Anatomy, Second University of Naples, Naples, Italy
  
• ISSN：1573-7373

文摘

Neuroblastoma (NB) is a paediatric tumor that arises from neural crest and shows heterogeneous clinical and biological features. The serine-protease high temperature requirement A1 (HtrA1) has a pivotal role in both cell proliferation and differentiation. Here we report the expression and localization of HtrA1 in NB tumor samples to assess HtrA1 role as a possible new biomarker of cellular differentiation in NB patients. HtrA1 protein expression by Western Blot assay was performed in 60 tissue samples of 50 children with NB and 10 children with ganglioneuroblastoma (GNB). HtrA1 was expressed in 56/60 (93.3?%) samples with different expression levels: low levels in 36/56 samples (64.3?%) and high levels in 20/56 (35.7?%). Higher levels were found in 1, 2 and 4s stages (80?%), whereas 3 and 4 stages (20?%) showed a low expression, with a statistically significant difference (p?=?0.003). Among not amplified N-MYC group, 28 (60?%) had low/absent expression of HtrA1: seven with recurrent disease and negative outcome and 21 in continuous complete remission (CCR), whereas all samples with high expression of HtrA1 (17/44) were in CCR (p?=?0.03). The immunohistochemical analysis showed localization of HtrA1 in differentiated areas higher than in undifferentiated areas where the protein was absent. Moreover, HtrA1 was highly expressed in all GNB samples. In conclusion, the over-expression of HtrA1 is correlated to cellular differentiation grade and stage of NB at diagnosis. Moreover, HtrA1 could represent a new marker of undifferentiation and biological aggressiveness of NB.