Analysis of novel tumor markers in pancreatic and biliary carcinomas using tissue microarrays
Analysis of novel tumor markers in pancreatic and biliary carcinomas using tissue microarrays
复制标题
DOI：
10.1016/j.humpath.2003.10.012
复制
发表时间：
2004-03-01
期刊：
影响因子：
3.3
通讯作者：
Argani, P
中科院分区：
文献类型：
--
作者：
Swierczynski, SL;Maitra, A;Argani, P
使用全球基因表达分析，多个新的肿瘤标志物过表达的浸润性导管腺癌的胰腺最近已被确定。然而，这些标志物在形态相似的胆管树腺癌中的表达尚未研究。本研究的目的有三个方面。首先，我们使用了8个已被证明是过表达的标记。在胰腺癌的全组织切片中，以验证从一系列胰腺癌产生的组织微阵列（TMA）（n = 68）。6种上皮标记物（肌成束蛋白、粘蛋白4、14-3-3sigma、前列腺干细胞抗原、拓扑异构酶II α和cdc 2/p34）的标记模式与先前发表的全组织切片研究一致，但需要的载玻片和试剂少得多。间皮素，一种上皮标记物，和热休克蛋白47，一种瘤周结缔组织增生的标记物，与整个组织切片相比，在TMAs中表现出较低的表达水平。第二，我们研究了以前未知的表达相同的8种新的肿瘤蛋白质的胆道系统的癌症，通过使用从一系列肝内胆管癌，胆囊腺癌，和腺癌的远端胆总管（n = 38）创建的TMA。8个标记物中的每一个在胆管癌中过表达，范围从14%证明至少与前列腺干细胞抗原的局部标记到100%与cdc 2/p34的标记。与胰腺癌相比，大多数标志物在胆道癌中的表达频率较低。此外，表达模式随胆道系统中的位置而变化（肝内与胆囊与胆总管远端）。这些差异对于间皮素、粘蛋白4和热休克蛋白47是统计学显著的（P < 0.05）。最后，检测了所选标记物在胆囊癌肿瘤进展中的表达。两种标记物，肌成束蛋白和间皮素，表现出表达上调，从原位癌过渡到浸润性腺癌，暗示了这些标记物在肿瘤进展中的作用。这项研究的结果表明，TMA技术提供了有效的和具有成本效益的手段来筛选大量的新的肿瘤标志物，即使在肿瘤，如胰腺癌和胆管腺癌，其特征是具有丰富的促纤维增生基质。此外，胰腺癌的新肿瘤标志物在胆管癌中显示相似但不相同的表达模式。因此，这些标记物在开发涉及胆道系统的肿瘤的诊断测试和治疗范例中是潜在有用的。
Using global gene expression analyses, multiple novel tumor markers overexpressed in infiltrating ductal adenocarcinomas of the pancreas have recently been identified. However, the expression of these markers in morphologically similar adenocarcinomas of the biliary tree has not been investigated. The purpose of the present study was 3-fold. First, we used 8 markers that have been shown to be overexpressed. in whole tissue sections of pancreatic adenocarcinomas to validate tissue microarrays (TMAs) created from a series of pancreatic adenocarcinomas (n = 68). The labeling patterns of 6 epithelial markers (fascin, mucin 4, 14-3-3sigma, prostate stem cell antigen, topoisomerase IIalpha, and cdc2/p34) were concordant with previously published studies on whole tissue sections, yet required far fewer slides and reagents. Mesothelin, an epithelial marker, and heat shock protein 47, a marker of peritumoral desmoplasia, showed lower levels of expression in the TMAs when compared with whole tissue sections. Second, we examined the previously unknown expression of the same 8 novel tumor proteins in cancers of the biliary tree by using TMAs created from a series of intrahepatic cholangiocarcinomas, gallbladder adenocarcinomas, and adenocarcinomas of the distal common bile duct (n = 38). Each of the 8 markers was overexpressed in the biliary cancers, ranging from 14% demonstrating at least focal labeling with prostate stem cell antigen to 100% labeling with cdc2/p34. Most of the markers showed lower frequencies of expression in the biliary tract carcinomas in comparison to the pancreatic adenocarcinomas. In addition, expression patterns varied with location in the biliary system (intrahepatic versus gallbladder versus distal common bile duct). These differences were statistically significant (P < 0.05) for mesothelin, mucin 4, and heat shock protein 47. Finally, the expression of selected markers in neoplastic progression of gallbladder cancer was examined. Two markers, fascin and mesothelin, showed up-regulation of expression with transition from carcinoma in situ to invasive adenocarcinoma, implicating a role for these markers in neoplastic progression. The results of this study indicate that TMA technology provides valid and cost-effective means to screen large numbers of novel tumor markers, even in tumors such as pancreatic and biliary adenocarcinomas that characteristically have abundant desmoplastic stroma. In addition, novel tumor markers of pancreatic adenocarcinomas show similar, yet not identical, expression patterns in biliary carcinomas. Therefore, these markers are potentially useful in developing diagnostic tests and treatment paradigms for tumors involving the biliary system.