GRP78 expression correlates with histologic differentiation and favorable prognosis in neuroblastic tumors.
Glucose-regulated protein 78 (GRP78), an endoplasmic reticulum protein, is essential for the differentiation of neuroblastoma cells and is selectively induced when the cells are undergoing apoptosis. These findings suggest that GRP78 may affect the tumor behavior of neuroblastoma. Our study evaluates the association of clinicopathologic factors and patient survival with the expression of GRP78 in patients with neuroblastoma. GRP78 expression in 68 neuroblastic tumors was investigated semiquantitatively by immunohistochemistry. GRP78 mRNA and protein levels in 7 tumor tissues were also quantified by real-time PCR and Western blot respectively and correlated well with the immunohistochemical results. Forty (58.8%) of the 68 neuroblastic tumors showed positive GRP78 expression. The percentage of positive GRP78 immunostaining increased as the tumor histology became differentiated (p = 0.001). Furthermore, positive GRP78 expression strongly correlated with early clinical stages (P = 0.002) but inversely correlated with MYCN amplification (p = 0.001). Kaplan-Meier analysis showed that patients with positive GRP78 expression did have better survival than those with negative expression (5-year survival rate, 72.9% and 23.4% respectively, p < 0.001). Multivariate analysis further showed that GRP78 expression was an independent prognostic factor. Moreover, GRP78 expression predicted better survival in patients with either undifferentiated or differentiated histologies. GRP78 expression still had significant prognostic value when the analysis was restricted to tumors of advanced stages or without MYCN amplification. Thus, GRP78 can serve as a novel independent favorable prognostic factor for patients with neuroblastoma.
Hsu
Wen-Ming
WM
Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
Hsieh
Fon-Jou
FJ
Jeng
Yung-Ming
YM
Kuo
Min-Liang
ML
Tsao
Po-Nien
PN
Lee
Hsinyu
H
Lin
Ming-Tsan
MT
Lai
Hong-Shiee
HS
Chen
Chiung-Nien
CN
Lai
Dar-Ming
DM
Chen
Wei-Jao
WJ
D001483:Base Sequence; D017931:DNA Primers; D000091342:Endoplasmic Reticulum Chaperone BiP; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D018832:Molecular Chaperones / Q000235:genetics*; D009447:Neuroblastoma / Q000235:genetics* / Q000401:mortality; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D016019:Survival Analysis; D013997:Time Factors
D017931:DNA Primers; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D012333:RNA, Messenger