摘要
Background/ Aims: In the natural history of gastric cancer, non- invasive neoplasia ( NiN) precedes invasive carcinoma. A histological classification of gastric NiN has recently been proposed by a World Health Organisation international panel of experts. Genetic instability is known to be among the molecular pathways involved in gastric oncogenesis. In this retrospective cross sectional study, microsatellite instability ( MSI) was analysed in a consecutive series of NiN and NiN related histological alterations from a northern Italian region at high risk for gastric cancer.
Patients/ Methods: Fifty five consecutive cases ( indefinite for NiN, 29 cases; low grade NiN, 17 cases; high grade NiN, nine cases) were analysed by radioactive polymerase chain reaction and electrophoresis for microsatellite alterations at six loci ( BAT25, BAT26, D2S123, D5S346, D17S250, and D3S1317). MSI was defined according to the Bethesda criteria distinguishing: ( 1) no instability in the analysed loci; ( 2) low frequency MSI ( MSI- L); and ( 3) high frequency MSI ( MSI- H). Immunohistochemical expression of MLH1 and MSH2 proteins was also analysed in all cases.
Results: Overall, MSI was found in 11 of 55 cases ( indefinite for NiN, five of 29 ( MSI- L, four; MSI- H, one); low grade NiN, three of 17 ( MSI- L, one; MSI- H, two); high grade NiN, three of nine ( MSI- L, one; MSI- H, two).
Conclusions: In an Italian high risk area for gastric cancer, MSI is part of the spectrum of genetic alterations in gastric non- invasive neoplasia. In European populations at high risk of gastric cancer, DNA repair system alterations are thought to be among the early molecular events in gastric carcinogenesis.
- 出版日期2005-8