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World J Gastroenterol. Jan 21, 2010; 16(3): 312-319
Published online Jan 21, 2010. doi: 10.3748/wjg.v16.i3.312
Helicobacter pylori and EBV in gastric carcinomas: Methylation status and microsatellite instability
Adriana Camargo Ferrasi, Nídia Alice Pinheiro, Silvia Helena Barem Rabenhorst, Otávia Luisa Caballero, Maria Aparecida Marchesan Rodrigues, Fabrício Carvalho, Celso Vieira Souza Leite, Marcia Valéria Pitombeira Ferreira, Marcos Aurélio Pessoa Barros, Maria Inês Moura Campos Pardini
Adriana Camargo Ferrasi, Nídia Alice Pinheiro, Maria Inês de Moura Campos Pardini, Blood Transfusion Center, Botucatu Medical School, UNESP - Sao Paulo State University, 18618-970 Botucatu-SP, Brazil
Silvia Helena Barem Rabenhorst, Marcia Valéria Pitombeira Ferreira, Marcos Aurélio Pessoa Barros, Department of Pathology - Federal University of Ceara, 60430-160 Fortaleza-CE, Brazil
Otávia Luisa Caballero, Ludwig Institute of Cancer Research, New York, NY 10065, United States
Maria Aparecida Marchesan Rodrigues, Department of Pathology, Medical School, UNESP - Sao Paulo State University, 18618-970 Botucatu-SP, Brazil
Fabrício de Carvalho, Ludwig Institute of Cancer Research, Sao Paulo-Brazil, 01323-903 Sao Paulo-SP, Brazil
Celso Vieira de Souza Leite, Department of Gastroenterology Surgery, Medical School, UNESP - Sao Paulo State University, 18618-970 Botucatu-SP, Brazil
Author contributions: Ferrasi AC, Pinheiro NA and Pardini MIMC designed the research; Ferrasi AC performed the research; Carvalho F and Caballero OL contributed new reagents and analytical tools; Ferrasi AC, Pinheiro NA, Pardini MIMC and Rabenhorst SHB analyzed the data; Barros MAP and Souza Leite CV provided specimens; Ferreira MVP and Rodrigues MAM contributed to the histopathological analyses.
Supported by FAPESP (in part) and CNPq, Brazill
Correspondence to: Maria Inês de Moura Campos Pardini, PhD, Blood Transfusion Center, Botucatu Medical School, UNESP - Sao Paulo State University, Distrito de Rubião Júnior, s/n, 18618-970 Botucatu-SP, Brazil. inespardini@gmail.com
Telephone: +55-14-38116041 Fax: +55-14-38116041
Received: July 29, 2009
Revised: September 11, 2009
Accepted: September 18, 2009
Published online: January 21, 2010
AIM: To verify the methylation status of CDH1, DAPK, COX2, hMLH1 and CDKN2A genes and to evaluate their association with Helicobacter pylori (H. pylori)-cagA+ and Epstein Barr virus (EBV) infections in gastric adenocarcinomas.
METHODS: Methylation-specific PCR (MSP) assay was performed in 89 primary gastric carcinomas (intestinal and diffuse types). Microsatellite instability (MSI) analysis was performed using the BAT26 primer set and PCR products were analyzed with the ABI PRISM 3100 Genetic Analyzer using Genescan 3.7 software (Applied Biosystems). Detection of H. pylori and genotyping were performed by PCR, using specific primers for ureaseC and cagA genes. The presence of EBV was assessed by in situ hybridization. Statistical analyses were performed using the χ2 or Fisher’s exact test.
RESULTS: The most frequent hypermethylated gene was COX-2 (63.5%) followed by DAPK (55.7%), CDH1 (51%), CDKN2A (36%) and hMLH1 (30.3%). Intestinal and diffuse adenocarcinomas showed different methylation profiles and there was an association between methylation of E-CDH1 and H. pylori-cagA+ in the intestinal adenocarcinoma type. MSI was correlated with hMLH1 methylation. There was an inverse correlation between DAPK hypermethylation and MSI.
CONCLUSION: We found a strong association between CDH1 methylation and H. pylori-cagA+ in intestinal-type gastric cancer, association of MSI and better prognosis and an heterogeneous COX-2 overexpression.
