Vauhkonen Matti, Vauhkonen Hanna, Sipponen Pentti
Department of Medicine, Helsinki University Central Hospital (HUCH), Jorvi Hospital, Espoo, Finland.
Best Pract Res Clin Gastroenterol. 2006;20(4):651-74. doi: 10.1016/j.bpg.2006.03.016.
Several attempts to classify gastric cancer (GCA) have been made over the past decades. Most successful, and widely used, is the classification by Laurén, which distinguishes, by microscopical morphology alone, two main cancer pathogeneses, diffuse (DGCA) and intestinal (IGCA) subtypes, which appear clearly as dissimilar clinical and epidemiological entities. Here we review the main differences in epidemiology, histopathology, and molecular pathology of the two main subtypes of gastric carcinomas based on Laurén classification. In clinical practice, however, clinical staging, particularly in predicting the survival, still remains superior to all classifications of gastric cancer independent of cancer type. The existence of local precursor lesions or conditions of IGCA tumours, i.e. Helicobacter pylori gastritis, atrophic gastritis (AG), intestinal metaplasia (IM), adenoma, dysplasia, and intramucosal neoplasia, is firmly established. The links of DGCA with intestinal-type epithelium, AG or IM are poor, or do not exist. So far, H. pylori gastritis is the only universal precursor condition for DGCA. It implies that AG and achlorhydria are of minor significance and infrequent in the development of DGCA but are important steps in that of IGCA. Despite an increasing body of data, the overall view on molecular pathology of GCA remains fragmentary. No consistent differences in the molecular pathology of GCA subtypes to meet the Laurén classification have been established. With the exception of TP53, no gene mutation occurring regularly in both histological types of GCA has been reported. Chromosomal aberrations and loss of heterozygosity seem to be non-specific and do not follow any consistent route in the progression of GCA. Microsatellite instability is more commonly found in IGCA than in DGCA. The present epigenetic data suggest that most of the decrease (or loss) of gene expression may be explained by promoter hypermethylation which is more often found in IGCA. In DGCA specific genes such as CDH1 are more often hypermethylated. Compared with GCA, in premalignant condition lesions gene mutations and chromosomal aberrations are infrequent. Epigenetic dysregulation might also represent a major mechanism for altered gene expression in premalignant stages in gastric carcinogenesis.
在过去几十年里，人们多次尝试对胃癌（GCA）进行分类。最成功且应用最广泛的是劳伦分类法，该分类法仅通过微观形态学区分两种主要的癌症发病机制，即弥漫型（DGCA）和肠型（IGCA）亚型，这两种亚型在临床和流行病学特征上明显不同。在此，我们基于劳伦分类法综述胃癌两种主要亚型在流行病学、组织病理学和分子病理学方面的主要差异。然而，在临床实践中，临床分期，尤其是在预测生存率方面，仍然优于所有胃癌分类，无论癌症类型如何。肠型胃癌肿瘤局部前体病变或状况的存在，即幽门螺杆菌胃炎、萎缩性胃炎（AG）、肠化生（IM）、腺瘤、发育异常和黏膜内瘤变，已得到确凿证实。弥漫型胃癌与肠型上皮、萎缩性胃炎或肠化生的联系较弱或不存在。到目前为止，幽门螺杆菌胃炎是弥漫型胃癌唯一普遍的前体状况。这意味着萎缩性胃炎和胃酸缺乏在弥漫型胃癌的发生中意义较小且不常见，但在肠型胃癌的发生中是重要步骤。尽管数据不断增加，但胃癌分子病理学的总体观点仍然支离破碎。尚未确立符合劳伦分类法的胃癌亚型分子病理学的一致差异。除TP53外，尚未报道在两种组织学类型的胃癌中均经常发生的基因突变。染色体畸变和杂合性缺失似乎是非特异性的，在胃癌进展过程中不遵循任何一致的途径。微卫星不稳定性在肠型胃癌中比在弥漫型胃癌中更常见。目前的表观遗传学数据表明，基因表达的大多数降低（或丧失）可能由启动子高甲基化解释，启动子高甲基化在肠型胃癌中更常见。在弥漫型胃癌中，特定基因如CDH1更常发生高甲基化。与胃癌相比，癌前病变中的基因突变和染色体畸变并不常见。表观遗传失调也可能是胃癌发生癌前阶段基因表达改变的主要机制。
