P53 gene and mismatch repair gene mutation status and clinical features in hepatocellular carcinoma patients

M Yano, MD,a T Asahara, MD,a K Katayama, MD,a T Itamoto, MD,a Y Hirai, PhD,b K Hamatani, PhD,b DG MacPhee, PhD,b

aDepartment of Surgery II, Hiroshima University School of Medicine, Hiroshima, Japan, bDepartment of Radiobiology, Radiation Effects Research Foundation, Hiroshima, Japan.

Aim: To investigate the correlation between p53 and mismatch repair gene mutation and long term outcome of hepatocellular carcinoma (HCC) patients, we analyzed 38 patients for mutations in p53 and mismatch repair gene (hMSH2). Methods: The patients group consisted of 32 men and 6 women; ages 46 to 77. Samples were obtained by surgically curative resection. Genomic DNA was extracted with phenol-chloroform. Mutations in the p53 and hMSH2 gene were analyzed by the PCR-SSCP method and the direct sequencing method. Results: Mutations of the hMSH2 gene were detected in 7 patients (18%), and mutations of the p53 gene were detected in 6 patients (16%). No mutation was observed in tumors less than 2 cm in diameter. There was a significant correlation between mutation and pathological factors of malignancy. The survival rate of patients with mutation-positive tumors was much poorer than those in patients with mutation-negative tumors. Eight of the 13 (62%) cases with mutation-positive tumors exhibited microsatellite instability, and 5 of the 25 (20%) cases with the mutation-negative tumors had microsatellite instability. Intrahepatic metastasis was common recurrent pattern in mutation-positive patients. However the recurrent pattern in mutation-negative patients was mainly multicentric recurrence. Conclusions: Our data suggest that mutations in the p53 or mismatch repair gene may closely correlate with the survival and recurrent pattern of HCC patients.

KEY WORDS: p53 gene, mismatch repair gene, hepatocellular carcinoma.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Gene Expression, Part 2.