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可切除性胰腺癌P19ARF、P16INK4a表达的临床意义

Expression of P19ARF and P16INK4a and their clinicopathological significance in human resectable pancreatic cancer
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摘要 目的 :了解P16INK4a(P16 )和P19ARF(P19)两种抑癌基因在可切除的人胰腺癌组织中的表达及其临床意义。方法 :胰腺癌切除标本 30例 ,用单克隆抗体免疫组化法同时测定P16和P19蛋白的表达 ,单变量和多变量分析P16、P19和主要临床病理指标对胰腺癌生存的影响。结果 :胰腺癌的P16、P19表达率分别为13.3%和 5 0 % ;P16与P19表达无相关性。P16的表达率与胰腺癌的临床病理分期和分级呈负相关 ;有大血管浸润的胰腺癌P19阳性率 (2 0 % )低于无血管浸润者 (72 .2 % ,P =0 .0 1)。P19在局部淋巴结阳性的胰腺癌表达率低于淋巴结阴性者 ,但无统计学意义。单变量分析显示 :肿瘤 >4cm、分期、大血管侵犯、3个以上的淋巴结转移及P16失表达是生存的不利因素 ;多变量分析则发现只有后四者才是独立的生存不利因素。结论 :P16的下调是胰腺癌发生发展的一个重要原因 ,是预后的独立的危险因素和胰腺癌生物学行为高度恶性的重要分子基础 ;P19下调与胰腺癌的大血管浸润和淋巴结转移有关 ,P19异常可能是胰腺癌播散的一种标示。 Objective:To investigate the expression and clinicopathological significance of P19ARF and P16INK4a in human resectable pancreatic cancer.Methods:Paraffin embedded surgical specimens from 30 cases of pancreatic cancer are used to detect P19ARF and P16INK4a proteins with monoclonal immunohistochemical ABC method. The influences of P19 and P16 on survived patients were tested by mono-and multivariate analysis.Results:P16 and P19 protein was detected in 4 of 30(13.3%) and 15 of 30(50%) cases in pancreatic cancer. No correlation was found between P16 and P19 in human pancreatic cancer. A negative correlations were found between the P16INK4a expression and clinicopathological staging as well as histological grading in pancreatic cancer. In pancreatic cancer,cases with major vascular invasion had a lower P19(20%) expression than those without(72.2%,P=0.01);those having local lymph node involvement also showed a lower expression of P19,but the differences didn't reach the statistical significant level. On monovariate analysis,size>4 cm,late staging,large vasculature involved,3 or more of lymph node metastasis and loss of expression of P16 were all negative factors to survival;but on multivariate analysis,only ture were the last 4 parameters.Conclusion:P16 downregulation seems to be an important event in tumor genesis and progression in pancreatic cancer,and it was an independent prognostic factor and an important molecular reason for its poor biological behavior in human resectable pancreatic cancer. We found for the first time that P19 might be a indicator of tumor local spread in pancreatic cancer.
出处 《肝胆胰外科杂志》 CAS 2004年第1期12-15,共4页 Journal of Hepatopancreatobiliary Surgery
关键词 胰腺癌 周期蛋白依赖激酶抑制剂 P16INK4A P19ARF pancreatic neoplasms cyclin-dependent kinase inhibitors P16INK4a P19ARF
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