RESUMO
BACKGROUND: The mechanisms promoting malignant transformation from chronic Helicobacter pylori-gastritis to gastric extranodal marginal zone lymphoma (MALT lymphoma) are insufficiently characterized. This follow-up study aimed to validate candidate microRNAs (miRs) in the process of neoplastic transformation. MATERIALS AND METHODS: MicroRNA expression signatures (n=20) were generated for a total of 60 cases of gastric lesions ranging from Wotherspoon 0-5 employing a quantitative real-time polymerase chain reaction (PCR) approach. Morphological and immunohistochemical characterization of the cohort was supplemented by PCR-based immunoglobulin heavy chain recombination studies. RESULTS: Quantitative expression of miR-150, miR-142.3p, miR-375 and miR-494 was significantly de-regulated in samples from MALT lymphoma compared to those from gastritis. CONCLUSION: The previously reported up-regulation of miR-150 in marginal zone lymphoma of MALT type was verified in an independent cohort of lymphoma samples employing a modified methodology. This further substantiates the role of miR-150 as a potential oncomiR in MALT lymphoma.
Assuntos
Linfoma de Zona Marginal Tipo Células B/genética , MicroRNAs/genética , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Doença Crônica , Gastrite/genética , Gastrite/metabolismo , Gastrite/microbiologia , Infecções por Helicobacter/genética , Infecções por Helicobacter/metabolismo , Infecções por Helicobacter/patologia , Helicobacter pylori/isolamento & purificação , Humanos , Imuno-Histoquímica , Linfoma de Zona Marginal Tipo Células B/metabolismo , Linfoma de Zona Marginal Tipo Células B/microbiologia , MicroRNAs/metabolismo , Inclusão em Parafina , Regulação para CimaRESUMO
The mechanisms underlying the transformation from chronic Helicobacter pylori gastritis to gastric extranodal marginal zone lymphoma (MALT lymphoma) are poorly understood. This study aims to identify microRNAs that might be involved in the process of neoplastic transformation. We generated microRNA signatures by RT-PCR in 68 gastric biopsy samples representing normal mucosa, gastritis, suspicious lymphoid infiltrates, and overt MALT lymphoma according to Wotherspoon criteria. Analyses revealed a total of 41 microRNAs that were significantly upregulated (n = 33) or downregulated (n = 8) in succession from normal mucosa to gastritis and to MALT lymphoma. While some of these merely reflect the presence of lymphocytes (e.g. miR-566 and miR-212) or H. pylori infection (e.g. miR-155 and let7f), a distinct set of five microRNAs (miR-150, miR-550, miR-124a, miR-518b and miR-539) was shown to be differentially expressed in gastritis as opposed to MALT lymphoma. This differential expression might therefore indicate a central role of these microRNAs in the process of malignant transformation.