Correlation of p53 Mutations and Microvascular Invasions of Hepatocellular Carcinoma: A Possible Factor of Poor Prognosis Following Surgical Resection

Korean J Hepatol > Volume 5(2); 1999 > Article

The Korean Journal of Hepatology 1999;5(2): 124-135.

Correlation of p53 Mutations and Microvascular Invasions of Hepatocellular Carcinoma: A Possible Factor of Poor Prognosis Following Surgical Resection

Kwang Hee Youn, M.D., Young-Hwa Chung, M.D., Soohyun Yang, M.D., Byung-Cheol Song, M.D., In Ran Hong, Jung A Kim, Yung Sang Lee, M.D., Dong Jin Suh, M.D., Eunsil Yu, M.D.1, Young-Joo Lee, M.D.2, Sung Gyu Lee, M.D.2

Department of Internal Medicine, diagnostic Pathology1, and General Surgery2 University of Ulsan College of Medicine Asan Medical Center, Seoul, Korea

ABSTRACT

Background/Aims
: p53 mutations have been reported to be a poor prognostic indicator in patients with HCC treated by surgical resection because of the association with frequent recurrence and shorter survival periods. Although poor differentiation of tumor has been considered to be associated with p53 mutation more frequently, the exact causes of unfavorable prognosis have not been clarified. Methods : To evaluate the relationship of p53 mutation and details of histological features, we examined 20 HCCs and surrounding liver tissues from the patients treated with surgical resection using direct sequencing of p53 gene at exons 5, 6, 7 and 8, and analyzed histopathologic features. We also analyzed the clinical, biochemical and radiological characteristics including the recurrences of tumor and survival periods in HCC patients with p53 mutant comparing to those with wild type p53 gene. Results : p53 mutants were found in 9 (45%) out of 20 resected HCC tissues, none from any surrounding tissues. p53 mutations were all point substitutions of a base; 5 in exon 8, 4 in exon 5 and 1 in exon 7. Between patients with mutants and those with wild type of p53 gene, there were no differences in age, sex, serum ALT, albumin, bilirubin and AFP levels, and HBV-positivity. HCCs with p53 mutants tended to be larger in size (14% in < 5 cm vs 67 % in > 5 cm; p=0.03) and multinodular in type (3/9 vs 0/11; p=0.07). p53 mutants tended to be found in poorly differentiated HCCs comparing to wild types. Even though there was no evidence of vascular or biliary invasion radiologically in all, 5 of 9 p53 mutant (+) (56%) and none of 11 p53-mutant (-) cases showed vascular invasions microscopically (p<0.01). However, there was no correlation between p53 mutations in tumor tissues and formation of capsules, biliary invasions or association with cirrhosis. During follow-up periods (median: 22;2 -28 mos) recurrences of HCC had been found in 6 of 9 patients with mutants (67%) in contrast to only 2 of 11 with wild types (18%)(p=0.07). Extrahepatic metastases were also common in patients with p53 mutant than those without it (56% vs 9%; p=0.05). Consequently, the 1 year cancer free survival rate of HCC patients with p53 mutant was significantly lower than that with wild type (44% vs 82%; p=0.02). Conclusions : Thus, it is suggested that p53 mutations tend to be commonly associated with microvascular invasions as well as poor differentiation microscopically, which may result in micrometastasis and frequent recurrences, and consequently shorter survival periods in HCC patents undergoing surgical resection. (Korean J Hepatol 1999;5:124－135)

KeyWords: p53 gene, Mutation, Hepatocellular carcinoma, Microvascular invasion