Calreticulin expression in neuroblastoma--a novel independent prognostic factor.
BACKGROUND
Calreticulin (CRT), an endoplasmic reticulum protein, has been reported to be essential for the differentiation of neuroblastoma (NB) cells, suggesting that CRT may affect the tumor behavior of neuroblastoma. The aim of this study was to evaluate the association of clinicopathologic factors and patient survival with the expression of CRT in patients with NB.


METHODS
Sixty-eight NBs were investigated by immunohistochemical staining against CRT, and were divided into positive and negative immunostaining groups. Correlations between calreticulin expression, various clinicopathologic and biologic factors, and patient survival were studied. In seven tumor samples, CRT mRNAs and proteins were evaluated with real-time PCR and western blot, respectively, and correlated with immunohistochemical findings.


RESULTS
Among 68 NBs, 32 (47.1%) showed positive CRT expression. Positive CRT immunostaining strongly correlated with differentiated histologies, as well as known favorable prognostic factors such as detected from mass screening, younger age (< or =1 year) at diagnosis and early clinical stages, but inversely correlated with MYCN amplification. Kaplan-Meier analysis revealed that NB patients with CRT expression did have better survival. Multivariate analysis demonstrated CRT expression to be an independent prognostic factor. Moreover, CRT expression also predicted better survival in patients with advanced-stage NBs, and its absence predicted poorer survival in patients whose tumor had no MYCN amplification. The amount of CRT mRNAs and proteins in NB tumor samples tested correlated well with the immunohistochemical expressions.


CONCLUSIONS
CRT expression correlates with the differentiation of NB and predicts favorable survival, thereby suggesting CRT to be a useful indicator for planning treatment of NB.
Hsu
W M
WM
Department of Surgery, National Taiwan University Hospital and College of Medicine, 7 Chung-Shan South Road, Taipei 100, Taiwan.
Hsieh
F J
FJ
Jeng
Y M
YM
Kuo
M L
ML
Chen
C N
CN
Lai
D M
DM
Hsieh
L J
LJ
Wang
B T
BT
Tsao
P N
PN
Lee
H
H
Lin
M T
MT
Lai
H S
HS
Chen
W J
WJ
D014408:Biomarkers, Tumor / Q000032:analysis*; D037282:Calreticulin / Q000096:biosynthesis*; D002454:Cell Differentiation; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D037282:Calreticulin