Sakellariou Stratigoula, Liakakos Theodore, Ghiconti Ioanna, Hadjikokolis Stamatis, Nakopoulou Lydia, Pavlakis Kitty
Pathology Department, G. Gennimatas Hospital, Papagou, Athens, Greece.
Anticancer Res. 2008 Mar-Apr;28(2A):1079-83.
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.
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.
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).
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.
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。
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。
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）。
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。
