Association of cyclin D1 expression with factors correlated with tumor progression in human hepatocellular carcinoma
Association of cyclin D1 expression with factors correlated with tumor progression in human hepatocellular carcinoma
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DOI：
10.1007/s005350050301
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发表时间：
1999-08-01
影响因子：
6.3
通讯作者：
Imai, K
中科院分区：
文献类型：
--
作者：
Sato, Y;Itoh, F;Imai, K
细胞周期蛋白 D1 基因（细胞周期 G1 至 S 期的正调控元件）的扩增和/或重排已在多种人类肿瘤中被报道，表明该基因具有致癌作用。在这项研究中，我们使用针对细胞周期蛋白 D1 的单克隆抗体 5D4 研究了 25 名患者的福尔马林固定和石蜡包埋的人肝细胞癌 (HCC) 组织中细胞周期蛋白 D1 的表达。在 HCC 细胞中观察到两种不同的染色模式：细胞核和细胞质。在所检查的 25 名 HCC 患者中，仅 2 名 (8%) 的组织中检测到细胞周期蛋白 D1 的核染色模式，并且在这些患者中没有发现特殊的临床病理特征。相比之下，在 25 名 HCC 患者中，有 8 名 (32%) 检测到细胞质染色模式，而没有核染色。细胞质cyclin D1的表达与门静脉癌栓（Vp）以及肝内转移（IM）患者存在显着相关性。这些结果表明细胞质cyclin D1的表达似乎与HCC的预后相关。细胞周期蛋白 D1 阳性和阴性患者的 Ag 核仁组织区 (NOR) 计数没有显着差异，表明细胞周期蛋白 D1 的免疫染色有可能成为人类 HCC 的独特预后标志物。在同系列HCC中使用p53抗体进行的同步免疫组化研究显示，88%的cyclin D1阳性患者也表达p53，而91%的p53阴性患者中，cyclin D1不表达。这些结果表明，在人类 HCC 的进展中，cyclin D1 的表达晚于 p53 的改变。
The amplification and/or rearrangement of the cyclin D1 gene, a positive regulatory element of the G1 to S phase, of the cell cycle, has been reported in various human tumors, suggesting an oncogenic role of this gene. In this study, we investigated the expression of cyclin D1 in the formalin-fixed and paraffin-embedded human hepatocellular carcinoma (HCC) tissues of 25 patients, using monoclonal antibody 5D4 raised against cyclin D1. Two distinct patterns of staining were observed in HCC cells, nuclear and cytoplasmic. The nuclear staining pattern of cyclin D1 was detected in the tissues of only 2 of the 25 HCC patients (8%) examined and no particular clinicopathological characteristics were found in these patients. In contrast, the cytoplasmic staining pattern, without nuclear staining, was detected in 8 of the 25 patients with HCC (32%). A significant correlation was found between the expression of cytoplasmic cyclin D1 and patients with tumor thrombus in the portal vein (Vp), as well as those with intrahepatic metastasis (IM). These results indicate that the cytoplasmic cyclin D1 expression appears to be related to the prognosis of HCC. The Ag nucleolar organizer regions (NORs) counts in cyclin D1-positive and -negative patients were not significantly different, suggesting that immunostaining for cyclin D1 has the potential to be a unique prognostic marker in human HCC. Simultaneous immunohistochemical study with p53 antibody in the same series of HCC revealed that 88% of the patients positive for cyclin D1 also expressed p53 and that in 91% of the patients negative for p53, cyclin D1 was not expressed. These results suggest that cyclin D1 is expressed later than the alteration of p53 in the progression of human HCC.