P15（INK4B）和SMAD4在进展期胃癌中的免疫组化表达
Immunohistochemical expression of P15 (INK4B) and SMAD4 in advanced gastric cancer.
作者信息
Sakellariou Stratigoula, Liakakos Theodore, Ghiconti Ioanna, Hadjikokolis Stamatis, Nakopoulou Lydia, Pavlakis Kitty
机构信息
Pathology Department, G. Gennimatas Hospital, Papagou, Athens, Greece.
出版信息
Anticancer Res. 2008 Mar-Apr;28(2A):1079-83.
BACKGROUND
P15 (a cyclin- D- kinase inhibitor) and SMAD4 (a signal transducer of the TGF-beta pathway) are two closely related proteins which may have an important role in gastric carcinogenesis.
MATERIALS AND METHODS
Sixty-three gastric carcinomas were studied. P15 and SMAD4 immunohistochemical expression was assessed with the DCS114.1 and BC/B8 mouse monoclonal antibodies, respectively. The results were tested for correlation with several clinicopathological parameters and patient survival.
RESULTS
Fifteen out of the 18 (83%) P15-positive tumors also exhibited preserved SMAD4 positivity (p = 0.001). Loss of P15 expression was more frequent in the intestinal type of carcinoma (p = 0.047). The survival rates were significantly higher for patients with reduced SMAD4 expression, in cases of well- or moderately differentiated tumors (p = 0.042).
CONCLUSION
P15 gene silencing might be an important event in the tumorigenesis of gastric adenocarcinomas of the intestinal type. Smad4 may behave as a tumor promoter in low grade tumors. The observed association between P15 and SMAD4 expression supports the inductive role of Smad4 in p15 transcription.
背景
P15（一种细胞周期蛋白D激酶抑制剂）和SMAD4（转化生长因子-β信号转导蛋白）是两种密切相关的蛋白，它们可能在胃癌发生中起重要作用。
材料与方法
对63例胃癌进行研究。分别用DCS114.1和BC/B8小鼠单克隆抗体评估P15和SMAD4的免疫组化表达。检测结果与几个临床病理参数及患者生存率的相关性。
结果
18例P15阳性肿瘤中有15例（83%）也表现出SMAD4阳性保存（p = 0.001）。P15表达缺失在肠型癌中更常见（p = 0.047）。在高分化或中分化肿瘤中，SMAD4表达降低的患者生存率显著更高（p = 0.042）。
结论
P15基因沉默可能是肠型胃腺癌肿瘤发生中的一个重要事件。Smad4在低级别肿瘤中可能起肿瘤促进作用。观察到的P15和SMAD4表达之间的关联支持Smad4在p15转录中的诱导作用。
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