Yang Xue, Takano Yasuo, Zheng Hua-Chuan
Department of Biochemistry and Molecular Biology and Institute of Pathology and Pathophysiology, College of Basic Medicine, China Medical University, Shenyang, P.R. China.
Oncol Lett. 2012 May;3(5):961-969. doi: 10.3892/ol.2012.628. Epub 2012 Mar 1.
Gastrointestinal adenocarcinoma (GIA) is a common malignant disease worldwide. Its tumorigenesis and progression is a multistage process with the involvement of a multifactorial etiology. Knowledge regarding altered expression of these genes during carcinogenesis may not only provide information about the molecular events during the initiation and progression of cancer, but may also result in the discovery of biological markers for the evaluation of cancer diagnosis and prognosis. In this review, we assessed molecular markers of pathogenesis, invasion, metastasis and prognosis, such as tumor suppressor and metastasis suppressor genes, and angiogenesis, cell adhesion, cell mobility, ER stress, mucin production, threonine protein kinase and REG family protein expression, by the establishment of tissue microarray (TMA) of GIA and immunohistochemistry (IHC) by intermittent microwave irradiation and in situ hybridization (ISH). Finally, we characterized the pathobiological features of Lauren's and WHO subtypes. It was found that the aberrant and cell-specific expression of these molecules is important in the malignant transformation of gastrointestinal epithelium and subsequent progression. These molecules also underlie the histogenic mechanisms of gastric carcinoma according to Lauren's and WHO classification. The combination of TMA, IHC and ISH may be widely applied to screen for molecular markers in GIA.
胃肠道腺癌(GIA)是一种全球常见的恶性疾病。其肿瘤发生和进展是一个多阶段过程,涉及多因素病因。关于这些基因在致癌过程中表达改变的知识,不仅可以提供有关癌症起始和进展过程中分子事件的信息,还可能导致发现用于评估癌症诊断和预后的生物标志物。在本综述中,我们通过建立GIA组织微阵列(TMA)以及采用间歇微波照射免疫组织化学(IHC)和原位杂交(ISH)技术,评估了发病机制、侵袭、转移和预后的分子标志物,如肿瘤抑制基因和转移抑制基因,以及血管生成、细胞黏附、细胞迁移、内质网应激、黏蛋白产生、苏氨酸蛋白激酶和REG家族蛋白表达。最后,我们对劳伦(Lauren)和世界卫生组织(WHO)亚型的病理生物学特征进行了描述。结果发现,这些分子的异常和细胞特异性表达在胃肠道上皮的恶性转化及后续进展中具有重要意义。根据劳伦和WHO分类,这些分子也是胃癌组织发生机制的基础。TMA、IHC和ISH的联合应用可能广泛用于筛选GIA中的分子标志物。