Low BAX protein expression correlates with disease recurrence in preoperatively irradiated rectal carcinoma.
OBJECTIVE
To determine the prognostic impact of BAX in correlation to its upstream effector p53 as well as clinicopathologic variables and patient outcome in preoperatively irradiated rectal carcinoma.


METHODS
We investigated 92 rectal carcinoma patients treated by preoperative radiotherapy to a total dose of 30 Gy followed by surgery. Median follow-up was 71 months. Immunohistochemistry was performed on paraffin sections of pretreatment biopsy samples for BAX protein. Also, we considered the previously determined p53 expression data from this cohort.


RESULTS
BAX protein expression was classified as high and low in 63 (68.5%) and 29 (31.5%) tumors, respectively. Unlike clinicopathologic variables, high BAX expression was significantly associated with improved disease-free survival by univariate analysis (p = 0.048). Moreover, in multivariate analyses, high BAX expression was an independent prognostic indicator for both improved local recurrence-free interval and improved disease-free survival (p = 0.03 and 0.047, respectively). Concerning the p53/BAX pathway, subgroup analysis yielded no association between p53 immunonegative/BAX high vs. p53 immunopositive/BAX low expressing tumors with regard to overall, disease-free, or local recurrence-free survival in either univariate (p = 0.88, 0.54, and 0.16, respectively) or multivariate analysis.


CONCLUSIONS
This study demonstrates that BAX protein expression might help to predict disease recurrence in preoperatively irradiated rectal carcinoma, whereas determination of p53, the proposed upstream regulator of BAX-induced apoptosis, did not provide additional prognostic information.
Nehls
Oliver
O
Department of Internal Medicine I, Eberhard-Karls-University Hospital of Tübingen, Tübingen, Germany. oliver.nehls@med.uni-tuebingen.de
Okech
Thomas
T
Hsieh
Chih-Jen
CJ
Sarbia
Mario
M
Borchard
Franz
F
Gruenagel
Hans-Helmut
HH
Gaco
Vera
V
Porschen
Rainer
R
Gregor
Michael
M
Klump
Bodo
B
D000230:Adenocarcinoma / Q000737:chemistry* / Q000401:mortality / Q000532:radiotherapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D012004:Rectal Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000532:radiotherapy; D013223:Statistics as Topic; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein