title: Expression of heat shock protein 70 in renal cell carcinoma and its relation to tumor progression and prognosis.
abstract: Heat shock proteins (HSPs) play an important role in the cellular response to environmental stress and exert a cytoprotective effect. Especially HSP70 is an effective inhibitor of apoptosis, suggesting a role of HSP70 in carcinogenesis and tumor progression. To explore the relevance of HSP70 in renal cell carcinomas (RCCs), we analyzed nuclear and cytoplasmic HSP70 protein expression in formalin-fixed tissue from 145 clear cell RCCs by immunohistochemistry as well as Western blot analysis. Nuclear HSP70 expression was found in all RCCs and 75% of the tumors also exhibited a cytoplasmic HSP70 staining. Importantly, RCCs showed significantly reduced cytoplasmic (p=0.001) and combined nuclear/cytoplasmic (p=0.0022) HSP70 expression when compared with their cells of origin. A significant (p=0.0176) decrease of nuclear HSP70 expression became evident from well to poorly differentiated clear cell RCCs. Quite similarly, a trend (p=0.0558) for reduced combined nuclear/cytoplasmic HSP70 expression was shown from early (pT1) to advanced (pT3) tumor stages. Nevertheless, no correlation between HSP70 expression and patients survival became evident. In conclusion, our investigation demonstrates a significant decrease of antiapoptotic HSP70 protein expression during carcinogenesis and during progression from well (G1) to poorly (G3) differentiated clear cell RCCs. Our results suggest that HSP70-mediated inhibition of apoptosis seems to be of minor importance for carcinogenesis and tumor progression in RCCs.
authors.affiliation: Institute of Pathology, Heinrich-Heine University Hospital, Duesseldorf, Germany. Ramp@med.uni-duesseldorf.de
authors.forename: U
authors.initials: U
authors.lastname: Ramp
authors.forename: C
authors.initials: C
authors.lastname: Mahotka
authors.forename: S
authors.initials: S
authors.lastname: Heikaus
authors.forename: T
authors.initials: T
authors.lastname: Shibata
authors.forename: M O
authors.initials: MO
authors.lastname: Grimm
authors.forename: R
authors.initials: R
authors.lastname: Willers
authors.forename: H E
authors.initials: HE
authors.lastname: Gabbert
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002452:Cell Count; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D003593:Cytoplasm / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005858:Germany / Q000453:epidemiology; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D018840:HSP70 Heat-Shock Proteins