p53 mutations in primary tumors and subsequent liver metastases are related to survival in patients with colorectal carcinoma who undergo liver resection

BACKGROUND, The appearance of p53 mutations in colorectal carcinoma was det ermined, independent of differentiation and tumor stage of the primary tumo rs, in relation to the survival of patients who were scheduled to undergo l iver resection. METHODS. Tumor material was analyzed for p53 mutations in primary colorecta l tumors and subsequent liver metastases from 41 consecutive patients who w ere scheduled to undergo surgical liver resection. DNA sequencing and immun ohistochemical staining of p53 protein within tumor nuclei were performed. RESULTS. Primary tumors displayed p53 mutations Within exons 5-9 in 41% of patients. No mutations were found in exons 4, 10, or 11. Forty-one percent of metastatic lesions had the same single mutation that was found in the pr imary tumor, whereas 11% of metastatic lesions had one additional mutation within exons 5-9; 22% had mutations only in their liver metastases, whereas corresponding primary tumors displayed wild-type p53. None of the patients had mutated p53 in their primary tumor and wild type in their metastases. Survival after undergoing liver resection was correlated negatively (P < 0. 05-0.01) with Duke Stages A-D classification of the primary tumors, tumor d ifferentiation, and radicality (> 0.7-0.8 mm) of resected liver metastases. CONCLUSIONS, The presence of p53 mutations in patients with metastatic lesi ons was related significantly (P < 0.003) to better survival after the pati ents underwent liver resection compared with patients with wild type p53 in their metastatic lesions. This finding was not related to covariates, such as Duke classification, tumor differentiation, type of liver metastasis, o r metastatic radicality during resections. Explanations for this unexpected finding remain unclear, although the authors speculate that occult tumor c ells with p53 mutations may be less responsive to growth factor(s) exposure during hepatic regeneration after resection. (C) 2001 American Cancer Soci ety.