Relevance of high virulence Helicobacter pylori strains and futility of CDX2 expression for predicting intestinal metaplasia after eradication of infection

Abstract

Objective. Different Helicobacter pylori genotypes are associated with distinct inflammatory responses and consequent development of pre-neoplastic lesions, namely intestinal metaplasia (IM), which is dependent on the expression of CDX2. We aimed to evaluate IM progression/regression in the context of H. pylori eradication, bringing into play the effect of the virulence of infecting H. pylori strains and the hypothesis that CDX2 expression might be a marker for later development of IM. Material and methods. Sixty-five male volunteers were evaluated by endoscopy before H. pylori eradication and after a median six-year follow-up. Histological diagnosis was performed at baseline and follow-up, and baseline H. pylori genotypes and CDX2 expression in non-metaplastic foci were also assessed. Results. Fifty-one individuals remained free from infection at follow-up. Six out of 27 who had no metaplastic lesions at baseline developed IM. CDX2 nuclear expression was observed in 15 of the 21 cases (71.4%) showing no progression to IM, and in three out of six cases (50%) with progression to IM (p = 0.367). Six of the 24 cases with IM at baseline showed regression to less severe outcomes, which was less frequent in those infected with high-virulence strains (7.7% vs. 50%, p = 0.047). In the latter there is a significant persistence of lymphoid follicles. Conclusions. Our results support that under infection with high virulence H. pylori strains, IM is a point of difficult return in the gastric carcinogenic pathway. The appearance of CDX-expressing cells in non-metaplastic foci was not associated with the development of IM during the six-year follow-up.

Key Words::

• CDX2
• chronic gastritis
• gastric carcinoma
• Helicobacter pylori
• intestinal metaplasia

Acknowledgements

This work was supported by the Fundação Calouste Gulbenkian (projects no. FC-54918 and FC-68697) and by Fundação para a Ciência e Tecnologia, Programa Operacional Ciência, Tecnologia e Inovação do Quadro Comunitário de Apoio III (Project PTDC/SAU-OBD/64490/2006), and the European Funding FEDER.

Declaration of interests: The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.

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