The prognostic significance of apoptosis-associated proteins BCL-2, BAX and BCL-X in clinical nephroblastoma.
Apoptotic cell death represents an important mechanism for the precise regulation of cell numbers in normal tissues. Various apoptosis-associated regulatory proteins, such as Bcl-2, Bax and Bcl-X, may contribute to the rate of apoptosis in neoplasia. The present study was performed to evaluate the prognostic value of these molecules in a group of 61 Wilms' tumours of chemotherapeutically pre-treated patients using an immunohistochemical approach. Generally, Bcl-2, Bax and for Bcl-X(S/L) were expressed in the blastemal and epithelial components of Wilms' tumour. Immunoreactive blastema cells were found in 53%, 41% and 38% of tumours for Bcl-2, Bax and for Bcl-X(S/L), respectively. An increased expression of Bcl-2 was observed in the blastemal component of increasing pathological stages. In contrast, a gradual decline of Bax expression was observed in the blastemal component of tumours with increasing pathological stages. Also blastemal Bcl-X(S/L) expression decreased with stage. Univariate analysis showed that blastemal Bcl-2 expression and the Bcl-2/Bax ratio were indicative for clinical progression, whereas epithelial staining was of no prognostic value. Multivariate analysis showed that blastemal Bcl-2 expression is an independent prognostic marker for clinical progression besides stage. These findings demonstrate that alterations of the Bcl-2/Bax balance may influence the clinical outcome of Wilms' tumour patients by deregulation of programmed cell death.
Ghanem
M A
MA
Department of Paediatric Urology, Josephine Nefkens Institute, The Netherlands.
Van der Kwast
T H
TH
Den Hollander
J C
JC
Sudaryo
M K
MK
Van den Heuvel
M M
MM
Noordzij
M A
MA
Nijman
R J
RJ
Soliman
E H
EH
van Steenbrugge
G J
GJ
D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism; D007680:Kidney Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D008297:Male; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000276:immunology / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000276:immunology / Q000378:metabolism*; D016896:Treatment Outcome; D009396:Wilms Tumor / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
C494826:BAX protein, human; C494811:BCL2L1 protein, human; D014408:Biomarkers, Tumor; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein