The mutator pathway is a feature of immunodeficiency-related lymphomas.

The mutator phenotype caused by defects in the mismatch repair system is observed in a subset of solid neoplasms characterized by widespread microsatellite instability-high (MSI-H). It is known to be very rare in non-Hodgkin lymphomas (NHL), whereas mutator NHL is the most frequent tumor subtype in mismatch repair-deficient mice. By screening a series of 603 human NHL with specific markers of the mutator phenotype, we found here 12 MSI-H cases (12/603, 2%). Of interest, we demonstrated that this phenotype was specifically associated with immunodeficiency-related lymphomas (ID-RL), because it was observed in both posttransplant lymphoproliferative disorders (9/111, 8.1%) and HIV infection-related lymphomas (3/128, 2.3%) but not in a large series of NHL arising in the general population (0/364) (P < 0.0001). The MSI pathway is known to lead to the production of hundreds of abnormal protein neoantigens that are generated in MSI-H neoplasms by frameshift mutations of a number of genes containing coding microsatellite sequences. As expected, MSI-H ID-RL were found to harbor such genetic alterations in 12 target genes with a putative role in lymphomagenesis. The observation that the MSI-H phenotype was restricted to HIV infection-related lymphomas and posttransplant lymphoproliferative disorders suggests the existence of the highly immunogenic mutator pathway as a novel oncogenic process in lymphomagenesis whose role is favored when host immunosurveillance is reduced. Because MSI-H-positive cases were found to be either Epstein-Barr virus-positive or -negative, the mutator pathway should act synergistically or not with this other oncogenic factor, playing an important role in ID-RL.

Helicobacter pylori-associated chronic gastritis and unexplained iron deficiency anemia: a reliable association?

BACKGROUND AND AIM: About 35% of iron deficiency anemia cases remain unexplained after a gastrointestinal evaluation. An association between Helicobacter pylori and iron malabsorption has been suggested. The aim of this study was to determine whether H. pylori-associated chronic gastritis is linked to unexplained iron deficiency anemia in adults. METHODS: From 1996 to 2001, we identified 105 patients with unexplained iron deficiency anemia after upper endoscopy, colonoscopy, small bowel radiographic examination and duodenal biopsies. Two biopsies were obtained from the gastric antrum and two from the corpus of each patient. Gastritis status was described according to the Sydney System and H. pylori infection was assessed by an immunohistochemical test on biopsy specimens. This group was compared to a control group matched for sex and age. RESULTS: There were 76 women and 29 men (mean age 57.4 +/- 21.4 years) examined in the study. A H. pylori-associated chronic gastritis was identified in 63 cases (60%) vs. 45 cases (43%) cases in the control group (p <.01). Atrophic gastritis was significantly associated with iron deficiency anemia compared with the control group [16 (15%) vs. 6 (6%); p <.03]. In the unexplained iron deficiency anemia group, (1) patients with chronic gastritis were significantly younger (52 +/- 22 vs. 64 +/- 20 years; p <.005), and (2) chronic gastritis was not linked to sex [sex ratio (male/female): 0.5 vs. 0.34, p =.34]. The prevalence of H. pylori infection was similar between premenopausal and postmenopausal women [28 (27%) vs. 26 (25%); p =.7] with iron deficiency anemia. CONCLUSION: H. pylori infection and chronic gastritis, especially atrophic gastritis, are significantly associated with unexplained iron deficiency anemia. Relationships between H. pylori-associated chronic gastritis and unexplained iron deficiency anemia should be considered.