Down-regulated p16 expression predicts poor prognosis in patients with extrahepatic biliary tract carcinomas.

Down-regulated p16 expression predicts poor prognosis in patients with extrahepatic biliary tract carcinomas.
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p16 表达下调预示肝外胆道癌患者预后不良。

DOI:
10.3892/ijo.20.3.453
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发表时间:
2002
影响因子:
5.2
通讯作者:
T. Fujimori
T. Fujimori
中科院分区:
医学2区
文献类型:
--
作者:
K. Ichikawa;J. Imura;H. Kawamata;J. Takeda;T. Fujimori

文献摘要

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肝外胆道癌(EBT)患者的预后普遍较差。我们用免疫组织化学方法评估了99例EBT患者手术切除的肿瘤标本中细胞周期蛋白依赖性激酶抑制因子p16的表达。我们还通过比较肿瘤的临床病理因素来检验p16的表达是否与肿瘤的生物学恶性有关。因此,我们发现p16在肿瘤细胞中的表达有三种类型:弥漫型、异质性和阴性型,其百分比分别为19%、41%和39%。异质性和阴性型p16表达下调,表现为尖锐(p=0.022)和浸润性生长(p=0.002)。此外,我们还发现p16表达下调的比例因肿瘤的位置不同而不同。我们还观察到,在部分肝外胆管癌患者中,p16表达下调的比例最高。相反,在预后较好的Vater壶腹区患者中,p16表达下调的比例最小,我们发现p16表达下调的患者预后最差,其预后仅限于Vater壶腹区。这些结果表明,p16表达下调被评估为预后不良的因素,p16表达的免疫组织化学模式也成为反映EBT患者生物学恶性程度的标志。
The prognosis of extrahepatic biliary tract cancer (EBT) patients is generally accepted to be poor. We immunohistochemically evaluated expression of p16, a cyclin-depend kinase inhibitor, in tumor specimens surgically removed from 99 EBT patients. We also examined whether there was any relationship between expression of p16 and biological malignancy of the tumor by comparing its clinicopathological factors. Consequently, we found that there were three types of p16 expression in the tumor cells; diffuse, heterogeneous and negative types, the percentages of which were 19, 41 and 39%, respectively. Heterogeneous and negative types, whose expression of p16 was considered to be down-regulated, showed scirrhous (p=0.022) and infiltrating growth (p=0.002). In addition, we found that the proportion of down-regulated expression of p16 was different, depending on the location of the tumor. We also observed that the down-regulated p16 expression was the highest in a proportion of patients with the extrahepatic bile duct carcinoma. In contrast, the proportion of down-regulated p16 expression was the least among the patients in the region of the ampulla of Vater with better prognosis, and we showed that the prognosis of patients with down-regulated expression of p16 was the poorest in terms of the cancer location where it is limited to the region of ampulla of Vater. These findings suggest that down-regulated p16 expression is evaluated as a factor of poorer prognosis and also that immunohistochemical pattern of p16 expression becomes a marker reflecting the biological malignancy of EBT patients.