Interaction of microsatellite instability and loss of heterozygosity in adenocarcinoma: Multiple markers in adenocarcinoma: An introduction to 'Genetic changes in Slovenian patients with gastric adenocarcinoma evaluated in terms of microsatellite DNA'

Gastric cancer, although only a fraction of gastrointestinal cancers, is a serious worldwide health concern still not understood because of several possible initiating mechanisms in the different forms of gastric adenocarcinomas. The current study by Gazvoda et al.,'Genetic changes in Slovenian patients with gastric adenocarcinoma evaluated in terms of microsatellite DNA', [1] evaluates how tumor status, type, histology and prognosis correlate with two genetic reporters linked with carcinogenesis: microsatellite instability (MSI) and loss of heterozygosity (LOH). On the basis of their findings, the current model of MSI interaction with LOH in cancer has become more complex indicating that several MSI/LOH markers might be needed both to explain steps in carcinogenesis, and to improve the diagnostic accuracy of this method. Additional epigenetic contributions (e.g. gene silencing), particularly within the mismatch repair system, might also contribute to this model. Gastric cancer is the second most frequent cause of cancer death worldwide, yet the precise mechanisms underlying the different subtypes of gastric carcinogenesis are poorly understood. Improvements in the diagnosis and prognosis of gastric cancer over classical clinicopathologic findings such as TNM stage, age or macroscopic tumor type, now include novel techniques for superficial endoscopic examination, and new strategies for genetically analyzing biopsied specimens. The development of gastric adenocarcinomas, such as that of many tumor classes, represents the cumulative effects of several different types of mutations, and it is now recognized that both the loss of normal DNA repair, as well as the mutation, loss or inhibition of tumor suppressor genes contribute to the genetic instability leading to cancer. It might be logically anticipated that the combined burden of these two defects would synergize in carcinogenesis, but the extent to which such pathways cooperate in promoting cancer is still not yet well understood. Clearly, an enhanced appreciation of the mechanisms and interactions of these pathways would aid development of diagnosis and treatment options.