Bcl-2 protein expression: association with p53 and prognosis in colorectal cancer.
Bcl-2 expression in colorectal carcinomas was studied in a series of 224 patients and the relation to p53 expression, stage and survival assessed. Bcl-2 expression was down-regulated compared with normal mucosa in 67% (151) of the cases. In 144 cases staining was positive for p53 (MAB DO7), and 41 of these 144 p53-positive cases were also bcl-2 positive (28%) compared with 32 of the remaining 80 p53-negative cases (40%). Survival was significantly worse (P = 0.01) in the p53-positive cases. Bcl-2-positive cases, including patients in all Dukes' stages, had a slightly better prognosis which was not statistically significant. However, cases at an early stage (Dukes' stages A and B) and with negative p53 status, had a much better prognosis if they showed bcl-2 protein expression, suggesting that the bcl-2 status itself has an effect on prognosis (P = 0.01). Neither bcl-2 nor p53 alone was correlated with stage, but when examined by both p53 and bcl-2 status a group [bcl-2(+)/p53(-)] with better prognosis was defined. The last group was significantly lower Dukes' stage, with 26 out of 32 cases (81%) being A or B compared with 22 (11%) of the 202 remaining cases (P = 0.004). Thus, either loss of bcl-2 expression or gain of abnormal p53 expression is associated with high stage and poor prognosis. The bcl-2(+)/p53(-) phenotype is similar to that of normal mucosa, and these results suggest that such cases represent an indolent group at an early stage in the progression of colorectal cancer.
University Department of Cellular Science, John Radcliffe Hospital, University of Oxford, UK.
L
L
Kaklamanis
A
A
Savage
R
R
Whitehouse
I
I
Doussis-Anagnostopoulou
S
S
Biddolph
P
P
Tsiotos
N
N
Mortensen
K C
KC
Gatter
A L
AL
Harris
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis*; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53