[Pathology and pathobiology of the gastric carcinoma]

Recent epidemiological studies in Serbia revealed that gastric carcinoma is the third and the fifth main cause of cancer morbidity in men and women, respectively. Despite the declining incidence of gastric cancer, it remains the second most common cause of cancer-related deaths as it is worldwide. A well-defined carcinogenic inflammation-metaplasia-dysplasia-cancer sequence typically precedes the development of most gastric adenocarcinomas. Alterations such as gastric mucosal atrophy and intestinal metaplasia are merely markers of increased risk, while gastric epithelial dysplasia (GED) represent a direct precursor of cancer. DNA damage and increased mucosal proliferation secondary to H pylori infection, combined with a suitable host susceptibility phenotype (eg, genetic polymorphisms in interleukin IL-1B, IL-1RN, and tumor necrosis factor a TNF-alpha genes), are important factors in this progression pathway. However, only a small minority of patients infected with H. pylori eventually develops gastric cancer, and eradication of H pylori in these patients does not seem to eliminate the risk of cancer completely. It has been shown that atrophy may be a better indicator of risk of cancer than intestinal metaplasia, and remains to be validated in routine clinical practice according to recent proposal for new quantitative methods. It is often associated with pseudopyloric gland metaplasia in the gastric corpus mucosa, which expresses a type of trefoil peptide, the spasmolytic polypeptide (termed spasmolytic polypeptide-expressing metaplasia or SPEM) and has been shown to be linked more closely to gastric cancer than intestinal metaplasia. Better histological characterization of adenomatous (or type I), hyperplastic (foveolar or type II) and tubule-neck (mucocellular or type III) GED, two-tiered grading system (low and high grade dysplasia) as well as the introduction of Padova and Vienna international classifications of dysplasia seem to be more helpful in GED surveillance and comparative studies. A combination of histopathological features, serum markers such as pepsinogen I, and molecular tests that analyze host susceptibility polymorphisms and bacterial virulence factors, may allow development of strategies for early detection of cancer in the future. At present, pathobiology of gastric cancerogenesis is far from known, despite the progressive knowledge on predisposing environmental conditions and genetic and epigenetic abnormalities, including tumour suppressor genes, oncogenes, microsatellite instability and hypermethylation or the significance of E-cadherin mutational status association with hereditary diffuse gastric cancer syndrome. Recent evidence regarding the importance of several histopathologically derived prognostic factors, such as resection margin status and lymph node metastases and their implications have also been discussed. We aim to review these aspects, with special relevance to gastric cancer specimen reporting.