Molecular pathology of gastric carcinoma: progress and prospects

Gastric carcinoma is the fourth most common malignancy in Western Europe and a major cause of cancer morbidity and mortality worldwide, particularly in the Far East and in areas of South America. The natural history of the disease is not fully established, and there is a need to elucidate the molecular mechanisms of gastric carcinogenesis in order to understand its pathogenesis and to develop molecular markers for clinical diagnostic use. Molecular analysis of colonic carcinogenesis has increased our understanding of its pathogenesis and has demonstrated multistage carcinogenesis in a human cancer. Research in gastric carcinoma has not achieved such significant progress, although a start has been made. We analyze some of the interpretation problems in molecular pathology affecting progress that are of interest to the histopathologist and review recent studies on the molecular biology of gastric carcinoma involving flow cytometry, cytogenetics, allele loss analysis, and transfection. We also summarize current knowledge about each of the major oncogenes and suppressor genes, attempting, in particular, to correlate gene abnormalities with morphologic appearances. The expanding field of cell proliferation and growth factors is outlined, gastric and colon carcinomas are compared, and gastric carcinoma is considered as a model system for the study of differentiation. This report concludes by suggesting directions for future research.