Hsu H C, Tseng H J, Lai P L, Lee P H, Peng S Y
Department of Pathology, College of Medicine, National Taiwan University, Taipei, Republic of China.
Cancer Res. 1993 Oct 1;53(19):4691-4.
To elucidate the biological significance of the p53 gene expression in human hepatocellular carcinoma (HCC), the p53 protein was studied in 184 resected unifocal primary HCCs, including 102 small (< or = 5 cm) and 82 large HCCs (> 5 cm), using immunocytochemistry. The p53 mRNA expression was analyzed in 69 cases using Northern hybridization. The p53 protein, which was detected in 58 HCCs (31.5%), was overexpressed more frequently in HCC with elevated serum alpha-fetoprotein level (37.9 versus 25%, P < 0.04), in large HCC (39.0 versus 25.5%, P < 0.03), and in invasive HCC (35.1 versus 13.3%, P < 0.01). The overexpression of p53 protein closely correlated with p53 mRNA overexpression (75 versus 44.4%, P < 0.003), and p53 gene mutation (76.9 versus 19.2%, P < 1 x 10(-9)). HCCs with p53 protein expression (group A) and those negative for both p53 protein and mRNA expression (group B) had an unfavorable outcome, while HCC with no p53 protein but with p53 mRNA overexpression (group C) had the best outcome; the 4-year survival was 26.1, 26.3, and 62.5%, respectively. The p53 gene mutation was significantly higher in group A HCC (76.9%) than in groups B (27.3%) and C (23.5%), P < 0.0001. The results suggest that the p53 protein and mRNA expression patterns in HCC correlate with p53 gene mutation and tumor behavior and may serve as a molecular prognostic factor.
为阐明p53基因表达在人类肝细胞癌（HCC）中的生物学意义，我们采用免疫细胞化学方法，对184例手术切除的单灶性原发性肝癌进行了p53蛋白研究，其中包括102例小肝癌（≤5cm）和82例大肝癌（>5cm）。采用Northern杂交法对69例病例进行了p53 mRNA表达分析。在58例肝癌（31.5%）中检测到p53蛋白，其在血清甲胎蛋白水平升高的肝癌中（37.9%对25%，P<0.04）、大肝癌中（39.0%对25.5%，P<0.03）以及浸润性肝癌中（35.1%对13.3%，P<0.01）的过表达更为频繁。p53蛋白的过表达与p53 mRNA过表达密切相关（75%对44.4%，P<0.003），也与p53基因突变密切相关（76.9%对19.2%，P<1×10⁻⁹）。有p53蛋白表达的肝癌（A组）以及p53蛋白和mRNA表达均为阴性的肝癌（B组）预后不良，而无p53蛋白但有p53 mRNA过表达的肝癌（C组）预后最佳；4年生存率分别为26.1%、26.3%和62.5%。A组肝癌（76.9%）的p53基因突变显著高于B组（27.3%）和C组（23.5%），P<0.0001。结果表明，肝癌中p53蛋白和mRNA表达模式与p53基因突变及肿瘤行为相关，可能作为一种分子预后因素。
