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간세포암 및 주위 간조직 내 Transforming Growth Factor-β1 mRNA 발현
서동진,김정아,이승규,정영화,양수현,송병철,이영주,정성애,이영상,홍인란,이재균 대한소화기학회 1999 대한소화기학회지 Vol.34 No.6
Background/Aims: Transforming growth factor-β1 (TGF-β1) has a central role in hepatic fibrosis and is also related to the development and progression of hepatocellular carcinoma (HCC). However, the effects of TGF-β1 overexpression in HCC remains unclear. This study was designed to assess the role of TGF-β1 in HCC. Methods: We semiquantitated TGF-β1 mRNA by competitive reverse transcription polymerase chain reaction from HCC and surrounding liver (SL) of 21 patients. We analyzed the relationship between TGF-β1 mRNA expression and clinicopathological characteristics to assess the role of TGF-β1 in HCC. Results: TGF-β1 mRNA was overexpressed in HCC than in SL (median 2.1×104 vs 5.1×103 copies/μg of RNA, p=0.01). TGF-β1 mRNA was overexpressed in all cases of well differentiated HCC. However, in the cases of poorly defferentiated HCC, the overexpression was observed in 57% of the patients (p=0.06). The overexpression occurred more frequently in single nodular type (87%) than in multinodular type (33%, also occurred in 100% of cases of tumor less than 3 cm, in 71% of cases of tumor sized between 3 and 5 cm, and in 50% of cases of tumor bigger than 5 cm (p=0.06). In addition, expression of TGF-β1 mRNA in HCC was inversely correlated with the level of serum α-fetoprotein (r=-0.47, p=0.03). Conclusions: TGF-β1 mRNA is generally overexpressed in HCC, suggesting that it may have important roles in the development of HCC. Our data also indicates that TGF-β1 mRNA expression may play more roles in small, single nodular and well differentiated HCC.
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이영주,서동진,유은실,김정아,윤광희,이승규,정영화,이영상,양수현,홍인란,송병철 대한간학회 1999 Clinical and Molecular Hepatology(대한간학회지) Vol.5 No.2
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 $lt; 5 cm vs 67 % in $gt; 5 cm; p=0.03) and multinodular in type (3/9 vs 0/11; p=0.07). p53 mutants tended to be found in poorly differentiated HCCs comparing to wild types. Even though there was no evidence of vascular or biliary invasion radiologically in all, 5 of 9 p53 mutant (+) (56%) and none of 11 p53-mutant (-) cases showed vascular invasions microscopically (p$lt;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)
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