Dynamic changes in p53 gene during metastasis and prognosis of colorectal carcimona / 中国组织工程研究

ABSTRACT

BACKGROUND: What role tumor-related genes play in the process of tumor generation, development, metastasis and prognosis has always been a thorny issue in medical field?OBJECTIVE: To study the detection of gene mutation in tumor by denaturing gradient gel electrophoresis(DGGE) and automated DNA se+uence analysis and the change of p53 gene and p53 protein during the development and metastasis of colorectal carcinoma so as to provide basis for evaluating the prognosis of colorectal carcinoma.DESIGN: Single sample study using the tissue specimen as subject.SETTING: Department of oncology in an affiliated hospital of a military medical university.PARTICIPANTS: We collected the primary focus and liver metastasis focus specimens from 41 patients with colon cancer who had hepatectomy because of liver metastasis 5 months to 5 years after radical operation for coloncancer. They were inpatients in Nanfang Hospital, First Military Medical University of Chinese PLA, from January 1994 to December 2000.METHODS: p53 gene(exons 5- 11) mutation of primary focus and liver metastasis focus specimens from 41 cases of colon cancer was examined by DGGE and automated DNA sequencing. Expression of p53 protein was detected by immunohistochemistry.histochemical staining.MAIN OUTCOME MEASURES:①Detection of the mutation of p53 gene by DGGE;②Analysis of p53 gene sequence;③Results of p53 immunohistochemical staining.RESULTS: p53 gene mutation was detected in exons 5 - 9 in 24 out of 41patients(62% ) . Among them, 6 patients had p53 mutation in liver metastasis. The others had consistent mutations in both primary coloreetal and hepatic metastatic lesions. In addition, p53 mutation was also found in the metastatic lesion in three patients. Among the 16 cases of mutation in primary colorectal and hepatic metastatic lesions, 14 cases showed that the ratio of p53 base peak to normal peak was significantly higher in hepatic metastatic lesions than in primary colorectal lesions(P ＜ 0. 001) . Results of p53 immunohistochemical staining were highly consistent with those of DGGE and DNA sequence analysis. However, gene analysis detected focus with nonsense mutation while immunohistochemistry detected overexpression of p53 protein.CONCLUSION: p53 mutation, in patients with colorectal carcinoma followed by hepatic metastases, mostly originates from primary colorectal lesion and then is kept and metastasizes into hepatic cells. The amount of mutated p53 gene and the number of tumor cells containing p53 mutation are increased in hepatic metastatic lesion. P53 mutation is positively correlated with overexpression of p53 protein.