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Published on: July 3, 2013
P21WAF1/CIP1 expression in colorectal carcinomas is related to Kras mutations and prognosis
Hiroyuki Mitomi1, Yasuo Ohkura, Naoshi Fukui
1Department of Clinical Research Laboratory (Pathology Division), National Hospital Organization Sagamihara Hospital, Sakura-dai, Sagamihara, Kanagawa, Japan. mitomi@sagamihara-hosp.gr.jp
Background/Aim:
P21WAF1/CIP1 is a cyclin-dependent kinase inhibitor activated by p53 to produce cell cycle arrest. A consensus has not been reached concerning the prognostic value of p21WAF1/CIP1 expression in colorectal cancers.
Patients/Methods:
P21WAF1/CIP1 expression was determined immunohistochemically in a series of 211 cases of colorectal carcinomas, together with its relation to p53, bcl-2, cell turnover (as assessed by Ki67 expression and apoptotic counts) and the Kras gene status. The expression of p21WAF1/CIP1 was also compared with reference to clinicopathological parameters and patient survival.
Results:
The median value for nuclear p21WAF1/CIP1 expression was 31% (interquartile range, 13-47%) and the fraction of cases considered to be high expressers (>20%) was 66%. Expression of p21WAF1/CIP1 was not associated with immunoreactivity for p53 or bcl-2, or cell turnover. P21WAF1/CIP1 high-expressing tumors were more often well differentiated (P<0.001), node-negative (P=0.037), Dukes' B (P=0.027) and Kras gene-mutated cases (P=0.04). On univariate analysis, low p21WAF1/CIP1 expressers (
Conclusion:
The regulation of p21WAF1/CIP1, independent of p53 or bcl-2 expression, appears to be associated with Kras mutations. The immunohistochemical detection of p21WAF1/CIP11 might thus be used to predict more precise outcome in colorectal cancer patients.
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