Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America.
PLoS One. 2013 Jun 11;8(6):e65144. doi: 10.1371/journal.pone.0065144. Print 2013.
Adenocarcinomas of the ampulla of Vater are classified as biliary cancers, though the exact epithelium of origin for these cancers is not known. We sought to molecularly classify ampullary adenocarcinomas in comparison to known adenocarcinomas of the pancreas, bile duct, and duodenum by gene expression analysis.
We analyzed 32 fresh-frozen resected, untreated periampullary adenocarcinomas (8 pancreatic, 2 extrahepatic biliary, 8 duodenal, and 14 ampullary) using the Affymetrix U133 Plus 2.0 genome array. Unsupervised and supervised hierarchical clustering identified two subtypes of ampullary carcinomas that were molecularly and histologically characterized.
Hierarchical clustering of periampullary carcinomas segregated ampullary carcinomas into two subgroups, which were distinctly different from pancreatic carcinomas. Non-pancreatic periampullary adenocarcinomas were segregated into two subgroups with differing prognoses: 5 year RFS (77% vs. 0%, p = 0.007) and 5 year OS (100% vs. 35%, p = 0.005). Unsupervised clustering analysis of the 14 ampullary samples also identified two subgroups: a good prognosis intestinal-like subgroup and a poor prognosis biliary-like subgroup with 5 year OS of 70% vs. 28%, P = 0.09. Expression of CK7+/CK20- but not CDX-2 correlated with these two subgroups. Activation of the AKT and MAPK pathways were both increased in the poor prognostic biliary-like subgroup. In an independent 80 patient ampullary validation dataset only histological subtype (intestinal vs. pancreaticobiliary) was significantly associated with OS in both univariate (p = 0.006) and multivariate analysis (P = 0.04).
Gene expression analysis discriminated pancreatic adenocarcinomas from other periampullary carcinomas and identified two prognostically relevant subgroups of ampullary adenocarcinomas. Histological subtype was an independent prognostic factor in ampullary adenocarcinomas.
Vater 壶腹腺癌被归类为胆道癌，尽管这些癌症的确切上皮起源尚不清楚。我们通过基因表达分析，旨在与已知的胰腺、胆管和十二指肠腺癌相比，对壶腹腺癌进行分子分类。
我们使用 Affymetrix U133 Plus 2.0 基因组芯片分析了 32 例新鲜冷冻切除的未经治疗的壶腹周围腺癌（8 例胰腺、2 例肝外胆管、8 例十二指肠和 14 例壶腹）。无监督和有监督的层次聚类确定了两种壶腹癌亚型，这些亚型在分子和组织学上均具有特征。
壶腹周围癌的层次聚类将壶腹癌分为两个亚组，这两个亚组与胰腺癌明显不同。非胰腺壶腹周围腺癌分为两个具有不同预后的亚组：5 年 RFS（77%比 0%，p=0.007）和 5 年 OS（100%比 35%，p=0.005）。14 例壶腹样本的无监督聚类分析也确定了两个亚组：具有良好预后的肠型亚组和具有较差预后的胆管型亚组，5 年 OS 分别为 70%和 28%，p=0.09。CK7+/CK20-而非 CDX-2 的表达与这两个亚组相关。不良预后的胆管型亚组中 AKT 和 MAPK 通路的激活均增加。在一个独立的 80 例壶腹验证数据集，只有组织学亚型（肠型与胰胆管型）在单因素（p=0.006）和多因素分析（p=0.04）中与 OS 显著相关。
基因表达分析将胰腺腺癌与其他壶腹周围癌区分开来，并确定了两种具有预后意义的壶腹腺癌亚组。组织学亚型是壶腹腺癌的独立预后因素。
