title: GRP78 expression correlates with histologic differentiation and favorable prognosis in neuroblastic tumors.
abstract: 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.
authors.affiliation: Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Wen-Ming
authors.initials: WM
authors.lastname: Hsu
authors.forename: Fon-Jou
authors.initials: FJ
authors.lastname: Hsieh
authors.forename: Yung-Ming
authors.initials: YM
authors.lastname: Jeng
authors.forename: Min-Liang
authors.initials: ML
authors.lastname: Kuo
authors.forename: Po-Nien
authors.initials: PN
authors.lastname: Tsao
authors.forename: Hsinyu
authors.initials: H
authors.lastname: Lee
authors.forename: Ming-Tsan
authors.initials: MT
authors.lastname: Lin
authors.forename: Hong-Shiee
authors.initials: HS
authors.lastname: Lai
authors.forename: Chiung-Nien
authors.initials: CN
authors.lastname: Chen
authors.forename: Dar-Ming
authors.initials: DM
authors.lastname: Lai
authors.forename: Wei-Jao
authors.initials: WJ
authors.lastname: Chen
mesh_terms: 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
chemical_list: D017931:DNA Primers; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D012333:RNA, Messenger