title: Glucose-regulated protein 78 positivity as a predictor of poor survival in patients with renal cell carcinoma.
abstract: BACKGROUND
  Glucose-regulated protein 78 (GRP78), a chaperone for newly formed proteins during folding and glycosylation, is associated with resistance to apoptosis in some forms of cancer. We assessed GRP78 expression and its correlation with clinicopathological parameters and survival.
  
  
  METHODS
  Immunohistochemistry was performed using formalin-fixed, paraffin-embedded specimens: 128 primary renal cell carcinoma (RCC) specimens (120 conventional and 8 other cell types) and 9 metastatic specimens. GRP78 positivity was determined based on intensity of staining and percentage of cells stained. Correlation of GRP78 positivity with clinicopathological parameters including patients' survival was evaluated.
  
  
  RESULTS
  A statistically significant association was found between GRP78 positivity and higher tumor grade (G3; p <0.0001), advanced T stage (≥pT3; p = 0.0002), lymphovascular invasion (positive; p <0.0001), regional nodal involvement (≥N1; p = 0.0086), and distant metastases at presentation (M1; p = 0.001). Positivity of GRP78 expression was significantly associated with shorter disease-specific survival and shorter progression-free survival. Cox proportional hazard model showed that strong GRP78 positivity was an independent predictor of shortened progression-free survival in N0M0 RCC patients.
  
  
  CONCLUSIONS
  There was a significant relationship between GRP78 expression levels and aggressiveness of RCC. Increased expression of GRP78 might be a useful parameter to predict shortened survival in patients with RCC.
authors.affiliation: Department of Urology, National Defense Medical College, Tokorozawa, Japan. kksmy @ sa2.so-net.ne.jp
authors.forename: Kenji
authors.initials: K
authors.lastname: Kuroda
authors.forename: Akio
authors.initials: A
authors.lastname: Horiguchi
authors.forename: Takako
authors.initials: T
authors.lastname: Asano
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ito
authors.forename: Junichi
authors.initials: J
authors.lastname: Asakuma
authors.forename: Akinori
authors.initials: A
authors.lastname: Sato
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Yoshii
authors.forename: Masamichi
authors.initials: M
authors.lastname: Hayakawa
authors.forename: Makoto
authors.initials: M
authors.lastname: Sumitomo
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Asano
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002292:Carcinoma, Renal Cell / Q000737:chemistry* / Q000401:mortality / Q000556:secondary / Q000601:surgery; D018572:Disease-Free Survival; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D006360:Heat-Shock Proteins / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D007564:Japan; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D016612:Paraffin Embedding; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D014408:Biomarkers, Tumor; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins