p16INK4a is a prognostic marker in resected ductal pancreatic cancer -: An analysis of p16INK4a, p53, MDM2, an Rb
p16INK4a is a prognostic marker in resected ductal pancreatic cancer -: An analysis of p16INK4a, p53, MDM2, an Rb
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DOI：
10.1097/00000658-200201000-00007
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发表时间：
2002-01-01
影响因子：
9
通讯作者：
Bartsch, DK
中科院分区：
文献类型：
--
作者：
Gerdes, B;Ramaswamy, A;Bartsch, DK
目的探讨胰腺导管癌（ductal pancreatic cancer，PC）患者G1/S期细胞周期调控基因p16（INK 4a）、p53、MDM 2和Rb的表达与预后的关系。MDM 2的作用在PC中没有明确定义。这些细胞周期调节剂的预后价值尚未澄清。方法62例PC与完整的后续谁进行了潜在的根治性切除术被列入本研究。对生存期最短的20例患者和生存期最长的20例患者进行极端组分析，检测p16、p53、MDM 2和Rb蛋白表达，并进行p16（INK 4a）和p53突变分析。p16（INK 4a）启动子超甲基化检查甲基化特异性polymerase chain reaction.Results显着更多的肿瘤中生存时间最短的患者有p1611的改变与肿瘤中生存时间最长的患者相比。与此相反，p53改变的频率在最短生存期组与最长生存期组中并不显著更高。MDM 2的稳定和Rb表达的损失被确定在少数的肿瘤，独立的生存length.Conclusions的存在下，p16（INK 4a）的改变切除肿瘤的PC患者与预后较差，表明患者可能受益于辅助治疗方案。p53改变、MDM 2过表达和Rb表达缺失不能作为本研究的预后标志物，但具有更大统计功效的更大研究可能显示关于p53的不同结果。
Objective To identify the prognostic relevance of the G1/S cell cycle regulator genes p16(INK4a), p53, MDM2, and Rb in patients with resected ductal pancreatic cancer (PC).Summary Background Data The tumor suppressor genes p16(INK4a), p53, and Rb are altered in PC in 27% to 95%, 40% to 70%, and 5%, respectively. The role of MDM2 is not clearly defined in PC. The prognostic value of these cell cycle regulators has not been clarified.Methods Sixty-two patients with PC with complete follow-up who underwent potentially curative resections were included in the study. An extreme group analysis was performed including the 20 patients with the shortest survival and the 20 patients with the longest survival, Protein expression of p16, p53, MDM2, and Rb was investigated, and mutation analysis of p16(INK4a) and p53 was performed. p16(INK4a) promoter hypermethylation was examined by methylation-specific polymerase chain reaction.Results Significantly more tumors in the shortest-surviving patients had p 1611 alterations compared with tumors of the longest-surviving patients. In contrast, the frequency of p53 alterations was not significantly higher in the shortest-surviving versus the longest-surviving groups. Stabilization of MDM2 and loss of Rb expression were identified in a minority of tumors, independent of survival length.Conclusions The presence of p16(INK4a) alterations in resected tumors of patients with PC is connected with a worse prognosis, indicating patients that might benefit from adjuvant therapy regimens. p53 alterations, MDM2 overexpression, and loss of Rb expression could not be identified as prognostic markers from this study, but a larger study with greater statistical power might show a different result with regard to p53.