Prognostische Relevanz von p21, p53 und deren Bedeutung als Response-Parameter für die adjuvante Therapie des kolorektalen Karzinoms

Background: The role of p53 and p21 as prognostic factors and response-parameters for adjuvant therapy in colorectal carcinomas are still under controversial debate. We aimed to evaluate the importance of both genes in a prospectively documented patient cohort. Patients and methods: Collection of follow-up data of 125 patients with sporadic colorectal carcinoma (stage UICC II/III), who underwent curative resection between 1995 and 2001. The median follow-up time was 51,8 ± 2,5 months. We investigated the protein expression of p53 and p21 in tumour tissues by immunohistochemistry. The probability of overall survival as a function of time was determined by the Kaplan-Meier method. Differences in survival curves were compared by the log rank test. Results: Patients had a 5-year overall survival rate of 64 % and a progression-free survival rate of 62 %. We observed an expression of p53 in 63 % and of p21 in 26 % of the carcinomas. In univariate survival analysis, p53 expression was associated with a significant better overall survival (p = 0,048). Negative p21 expression was significantly related to a better progression-free (82,4 ± 4,8 months; p = 0,02) and overall survival (83,9 ± 4,5 months; p = 0,005). In a subgroup analysis, we found a significant survival advantage for patients with p21-negative/p53-positive carcinomas. The progression-free survival was 86,5 ± 5,9 months (p = 0,007) and the overall survival 94,5 ± 5,0 months (p < 0,0001) as compared to other subgroups p21−/p53−, p21+/p53+, p21+/p53−. Adjuvant therapy revealed a benefit in overall survival in patients with p21-negative carcinomas as compared to patients without therapy (90,7 ± 4,7 vs. 58,3 ± 6,1 months, p = 0,017). Patients with p21-negative/p53-positive carcinomas had a favourable overall survival after adjuvant therapy (99,4 ± 4,8 vs. 66,9 ± 6,8 months, p = 0,012). Conclusion: The cell cycle regulator p21 has prognostic impact on patient survival as well as effects on adjuvant therapy. Moreover, the combination of p21−/p53+ expression in colorectal carcinomas might be particularly important.