p53 and Bcl-2 as significant predictors of recurrence and survival in rectal cancer.
The aim of this study was to evaluate the prognostic value of p53 nuclear accumulation and Bcl-2 expression after curative surgery for rectal cancer. Immunohistochemistry was performed using monoclonal antibodies (MAb) (DO-1 for p53; anti-human Bcl-2 MAb, clone 124, for Bcl-2) on formalin-fixed, paraffin-embedded tissues of 160 rectal carcinomas (UICC stages I-III), and results were compared with data from the prospective registry of rectal cancer by univariate and multivariate logistic regression model focusing specifically on recurrence. Survival was calculated by the Kaplan-Meier method and proportional hazards model. p53 nuclear accumulation was documented in 39% (n=63) of tumours and was associated with a higher incidence of tumour progression (local or distant recurrence) and poorer disease-free survival (P<0.0001). Bcl-2 expression was detected in 29% (n=47), and was associated with longer disease-free survival and lower incidence of recurrence (P<0.0086). Multivariate logistic regression analysis demonstrated that gender (P=0.0136), UICC stage (P=0.0002), p53 expression (P=0.0002) and Bcl-2 expression (P=0. 0243) were independent factors predictive of recurrence. The proportional hazards model identified p53 (P=0.0009), UICC stage (P=0.0480), gender (P=0.0049), but not Bcl-2 (P=0.1503), as independently related to disease-free survival. Looking at the p53/Bcl-2 subgroups, the poorest prognosis was observed in the p53+/Bcl-2- subgroup, whereas patients whose tumours were p53-/Bcl-2+ had the best prognosis (P<0.0001). Immunohistochemical assessment of both p53 and Bcl-2 status may be valuable in predicting recurrence and survival after curative surgery for rectal cancer. Therefore, they play a role as prognostic factors in rectal cancer. p53 is a stronger predictor of prognosis than Bcl-2.
Schwandner
O
O
Department of Surgery, Medical University of Luebeck, Ratzeburger Allee 160, D-23538, Luebeck, Germany. ao.schwandner@t-online.de
Schiedeck
T H
TH
Bruch
H P
HP
Duchrow
M
M
Windhoevel
U
U
Broll
R
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis*; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D012004:Rectal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D012737:Sex Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53