ORIGINAL ARTICLE

Microsatellite instability and gastric non-invasive neoplasia in a high risk population in Cesena, Italy

M Rugge¹, G Bersani², R Bertorelle¹, G Pennelli¹, V M Russo³, F Farinati⁴, D Bartolini⁵, M Cassaro¹ and V Alvisi⁶

¹ Department of Oncology and Surgical Sciences, University of Padova, I-35121 Padova, Italy
² Gastroenterology Unit, Malatesta-Novello Hospital, I-47023 Cesena, Italy
³ Department of Pathology, San Luigi Hospital, I-95100 Catania, Italy
⁴ Department of Gastroenterology and Surgical Sciences, University of Padova, I-35128 Padova, Italy
⁵ Department of Pathology, Maurizio Bufalino Hospital, I-47023 Cesena, Italy
⁶ School of Gastroenterology, University of Ferrara, I-47023 Cesena, Italy

Correspondence to:
Correspondence to:
Dr M Rugge
Cattedra di Anatomia Patologica, Department of Oncology and Surgical Sciences, Università degli Studi di Padova, Via Aristide Gabelli, 61, I-35121 Padova, Italy; massimo.rugge{at}unipd.it

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.

Abbreviations: GC, gastric cancer; MSI, microsatellite instability; MSI-H/L, high/low frequency of microsatellite instability; MSS, microsatellite stable; NiN, non-invasive neoplasia; PCR, polymerase chain reaction; WHO, World Health Organisation

Keywords: gastric non-invasive neoplasia; microsatellite instability; gastric cancer; microsatellite instability and precancerous gastric lesions

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