Departments of Pathology, Alexandria, Egypt.
Chin J Cancer Res. 2013 Jun;25(3):281-8. doi: 10.3978/j.issn.1000-9604.2013.04.02.
Although p21 ras has been reported to be upregulated in hepatocellular carcinoma complicating chronic hepatitis C type I, p21 ras has a different role in advanced stages, as it has been found to be downregulated. The goal of this study was to investigate the status of p21 ras in early-stage/low-grade and late-stage/high-grade hepatocellular carcinoma and its possible link to apoptosis.
Thirty-five cases each of chronic HCV hepatitis type 4 (group I) and cirrhosis with hepatocellular carcinoma (HCC) complicating chronic HCV hepatitis (groups II and III) were immunohistochemically evaluated using a p21 ras polyclonal antibody. The apoptotic index was determined in histologic sections using the terminal deoxynucleotidyl transferase-mediated d-UTP biotin nick end labeling (TUNEL) assay.
Significant differences (P=0.001) were detected in p21 ras protein expression between the three groups. A near 2-fold increase in p21 ras staining was observed in the cirrhotic cases compared to the hepatitis cases, and p21 ras expression was decreased in the HCC group. p21 ras expression correlated with stage (r=0.64, P=0.001) and grade (r=(-)0.65, P=0.001) in the HCC group and grade in the HCV group (r=0.44, P=0.008). Both p21 ras expression and TUNEL-LI were significantly lower in large HCCs compared to small HCCs (P=0.01 each). The TUNEL values were negatively correlated with stage in the HCC group (r=(-)0.85, P=0.001). The TUNEL values were also negatively correlated with grade in both the HCV and HCC groups (r=0.89, P=0.001 and r=(-)0.53, P=0.001, respectively). The p21 ras scores were significantly correlated with the TUNEL-LI values in the HCC group (r=0.63, P=0.001) and HCV group (r=0.88, P=0.001).
p21 ras acts as an initiator in HCC complicating type 4 chronic HCV and is downregulated with HCC progression, which most likely promotes tumor cell survival because it facilitates the downregulation of apoptosis with tumor progression.
虽然已报道 p21 ras 在合并慢性丙型肝炎的肝细胞癌中上调，但 p21 ras 在晚期具有不同的作用，因为它已被发现下调。本研究的目的是研究早期/低级别和晚期/高级别肝细胞癌中 p21 ras 的状态及其与细胞凋亡的可能联系。
使用 p21 ras 多克隆抗体对 35 例慢性丙型肝炎病毒 4 型（I 组）和合并慢性丙型肝炎病毒的肝硬化伴肝细胞癌（II 组和 III 组）患者进行免疫组织化学评估。使用末端脱氧核苷酸转移酶介导的 d-UTP 生物素缺口末端标记（TUNEL）测定法在组织学切片中确定凋亡指数。
在三组之间检测到 p21 ras 蛋白表达的显著差异（P=0.001）。与肝炎病例相比，肝硬化病例中 p21 ras 染色增加近 2 倍，而 HCC 组中 p21 ras 表达减少。p21 ras 表达与 HCC 组的分期（r=0.64，P=0.001）和分级（r=（-）0.65，P=0.001）以及 HCV 组的分级相关（r=0.44，P=0.008）。与小 HCC 相比，大 HCC 中的 p21 ras 表达和 TUNEL-LI 均显著降低（P=0.01）。在 HCC 组中，TUNEL 值与分期呈负相关（r=（-）0.85，P=0.001）。TUNEL 值也与 HCV 和 HCC 组的分级呈负相关（r=0.89，P=0.001 和 r=（-）0.53，P=0.001）。在 HCC 组（r=0.63，P=0.001）和 HCV 组（r=0.88，P=0.001）中，p21 ras 评分与 TUNEL-LI 值显著相关。
p21 ras 在合并 4 型慢性丙型肝炎的肝细胞癌中充当启动子，并且随着肝癌的进展而下调，这很可能促进肿瘤细胞的存活，因为它促进了随着肿瘤进展的细胞凋亡的下调。
