Uozaki Hiroshi, Barua Rita Rani, Minhua Sun, Ushiku Tetsuo, Hino Rumi, Shinozaki Aya, Sakatani Takashi, Fukayama Masashi
Department of Pathology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Int J Clin Exp Pathol. 2011 Mar;4(3):230-40. Epub 2011 Mar 1.
Gastric cancer (GC) is a major cancer, sometimes associated with Epstein-Barr virus (EBV). Some transcriptional factors (TFs) are specific to the digestive tract and related to the character of the tumors.
We studied three TFs, SOX2, CDX2, and hepatocyte nuclear factor 4 alpha-promoter 1 (HNF4aP1) in GC. First, 255 tumors including 31 EBV-associated GC were immunohistochemically examined using tissue arrays and compared TF type and mucin phenotype. We classified them into 4 TF types: N-TF type as SOX2-/HNF4aP1- tumor, G: SOX2+/HNF4aP1-, GI: SOX2+/HNF4aP1+, and I: SOX2-/HNF4aP1+. Next, 915 GCs were intensely investigated and compared with their clinicopathological factors.
In the first study, 255 GCs were classified into N-TF 44%, G-TF 31%, GI-TF 3%, and I-TF 2%. The TF type did not strictly accord with the mucin phenotype, classified by MUC2/5AC/6/CD10 expression. EBV status was the only factor related to both the TF and mucin phenotype classifications (P<0.0001, <0.0001). TF classification is related to more factors including tumor stage, than mucin phenotype classification. The second study using 915 GCs revealed that N-TF gradually increased and I-TF decreased as GC invaded deeper. TF classification was not related to nodal involvement in each tumor stage. HNF4aP1 and CDX2 were independent factors for early stage tumor in logistic regression analysis.
EBV-associated GC is a discriminating group in both TF and mucin phenotype. TF classification, especially the absence of HNF4aP1 and CDX2, is related to tumor invasion. TF classification is a useful marker to study the carcinogenesis of GC further.
胃癌（GC）是一种主要的癌症，有时与爱泼斯坦-巴尔病毒（EBV）相关。一些转录因子（TFs）对消化道具有特异性且与肿瘤特征相关。
我们研究了胃癌中的三种转录因子，即SOX2、CDX2和肝细胞核因子4α启动子1（HNF4aP1）。首先，使用组织芯片对包括31例EBV相关胃癌在内的255例肿瘤进行免疫组织化学检查，并比较转录因子类型和黏蛋白表型。我们将它们分为4种转录因子类型：N-TF型为SOX2-/HNF4aP1-肿瘤，G型：SOX2+/HNF4aP1-，GI型：SOX2+/HNF4aP1+，以及I型：SOX2-/HNF4aP1+。接下来，对915例胃癌进行了深入研究，并与它们的临床病理因素进行比较。
在第一项研究中，255例胃癌被分为N-TF型44%，G-TF型31%，GI-TF型3%，I-TF型2%。转录因子类型与通过MUC2/5AC/6/CD10表达分类的黏蛋白表型并不严格一致。EBV状态是与转录因子和黏蛋白表型分类均相关的唯一因素（P<0.0001，<0.0001）。与黏蛋白表型分类相比，转录因子分类与更多因素相关，包括肿瘤分期。使用915例胃癌的第二项研究表明，随着胃癌浸润深度增加，N-TF型逐渐增加而I-TF型减少。转录因子分类与各肿瘤分期的淋巴结受累无关。在逻辑回归分析中，HNF4aP1和CDX2是早期肿瘤的独立因素。
EBV相关胃癌在转录因子和黏蛋白表型方面都是一个有区别的群体。转录因子分类，尤其是HNF4aP1和CDX2的缺失，与肿瘤浸润相关。转录因子分类是进一步研究胃癌致癌机制的有用标志物。
