Expression and localization of serine protease Htra1 in neuroblastoma: correlation with cellular differentiation grade.
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.
Pediatric Oncology Service, Pediatric Department, Second University of Naples, Naples, Italy.
Velia
V
D'Angelo
Giulia
G
Pecoraro
Paolo
P
Indolfi
Adriana
A
Iannotta
Vittoria
V
Donofrio
Maria Elena
ME
Errico
Cristiana
C
Indolfi
Maria
M
Ramaglia
Angela
A
Lombardi
Martina
M
Di Martino
Vincenzo
V
Gigantino
Alfonso
A
Baldi
Michele
M
Caraglia
Antonio
A
De Luca
Fiorina
F
Casale
D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D002454:Cell Differentiation; D002648:Child; D002675:Child, Preschool; D005260:Female; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000201:enzymology* / Q000473:pathology*; D012697:Serine Endopeptidases / Q000378:metabolism*
D014408:Biomarkers, Tumor; D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases