Pathogenesis of Gastric Cancer

Abstract

Gastric cancer (GC) is still the fifth most common cancer worldwide despite a steady decline in its incidence over the last decades. GC is a heterogeneous disease. Its incidence varies by geography, among different ethnic groups, and by gender. The etiology of GC is multifactorial and related to dietary factors, environmental factors including infectious organisms, as well as hereditary factors. The vast majority of GCs are adenocarcinomas which are classified based on the disease stage as early or advanced stage. Early-stage GCs are macroscopically distinct from advanced stage GC, but both are similar based on histology. GC is histologically heterogeneous which is reflected in the large number of proposed histological classification systems. The most commonly used classification in the West is that by Lauren which has two main categories: intestinal type and diffuse type, whereas Nakamura’s classification into differentiated and undifferentiated type is popular in Japan due to its inclusion in decision algorithms for endoscopic resections. The histologically defined precursor lesion of intestinal-type GC is gastric dysplasia, also referred to as intraepithelial neoplasia. Histologically defined precursor lesions for sporadic diffuse-type GC have not been well described which is in contrast to hereditary diffuse-type gastric cancer, where in situ carcinoma is commonly seen. Recent molecular studies in GC have confirmed that the molecular makeup of GC is also heterogeneous and suggest that there are distinct molecularly identifiable subgroups of GC with clinical relevance which cannot be identified based on histology, adding a new level of complexity when developing a clinically relevant GC classifier that ultimately improves patient outcome.