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.
Kaklamanis
L
L
University Department of Cellular Science, John Radcliffe Hospital, University of Oxford, UK.
Savage
A
A
Whitehouse
R
R
Doussis-Anagnostopoulou
I
I
Biddolph
S
S
Tsiotos
P
P
Mortensen
N
N
Gatter
K C
KC
Harris
A L
AL
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