Bcl-2 protein expression: association with p53 and prognosis in colorectal cancer

Abstract

Summary 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 D07), and 41 of these 144 p53-positive cases were also bcl-2 positive (28%) comeared 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.

Analysis of p53/BAX in primary colorectal carcinoma: Low BAX protein expression is a negative prognostic factor in UICC stage III tumors

“…43,44 This correlation was not evident in a larger series of 238 patients. 46 Possibly, high Bcl-2 expression in colorectal cancer is rather associated with low grading and low tumor stage 44,47 than with prognosis or p53 status per se.…”

“…As expected, these studies did not see a correlation between p53 alterations and Bcl-2 expression. [43][44][45][46] Paradoxically, patients with tumors expressing Bcl-2 and not p53, were found to have a better prognosis. 43,44 This correlation was not evident in a larger series of 238 patients.…”

“…[43][44][45][46] Paradoxically, patients with tumors expressing Bcl-2 and not p53, were found to have a better prognosis. 43,44 This correlation was not evident in a larger series of 238 patients. 46 Possibly, high Bcl-2 expression in colorectal cancer is rather associated with low grading and low tumor stage 44,47 than with prognosis or p53 status per se.…”

Clinical significance of prognostic and predictive markers in colorectal cancer

“…Studies of at least 100 patients with CRC using p53 monoclonal antibodies have generally found that p53 overexpression was associated with worse prognosis. 5,6 This association has not been a consistent observation as some studies have found the opposite, 7 or no correlation. 8,9 However, the majority of DNA sequencing studies have shown a significantly shorter survival time in patients with mutant p53.…”

An expression of interest

“…For example, expression of Bcl-2 delays mammary tumor formation in dimethylbenz(a)anthracene treated mice 21 and hepatocellular carcinoma in c-myc transgenic mice. 22 Studies of human colon cancer [23][24][25][26][27] and breast cancer 28 have demonstrated that Bcl-2 expression is associated with improved survival. For Bax, increased expression in transgenic mice is associated with increased apoptosis and a paradoxical acceleration in lymphoma development in p53 À/À mice.…”