Expression of CD86 and increased infiltration of NK cells are associated withHelicobacter pylori-dependent state of early stage high-grade gastric MALT lymphoma

Abstract

Abstract Abstract AbstractAIM: A high percentage of early-stage high-grade gastric mucosa-associated lymphoid tissue (MALT) lymphomas remain Helicobacter pylori (H pylori)-dependent. However, unlike their low-grade counterparts, high-grade gastric MALT lymphomas may progress rapidly if unresponsive to H pylori eradication. It is mandatory to identify markers that may predict the H pylori-dependent status of these tumors. Proliferation of MALT lymphoma cells depends on cognate help and cell-to-cell contact of H pylori-specific intratumoral T-cells. To examine whether the expression of co-stimulatory marker CD86 (B7.2) and the infiltration of CD56 (+) natural killer (NK) cells can be useful markers to predict H pylori-dependent status of high-grade gastric MALT lymphoma. METHODS:Lymphoma biopsies from 26 patients who had participated in a prospective study of H pylori-eradication for stage I E high-grade gastric MALT lymphomas were evaluated. Tumors that resolved to Wotherspoon grade II or less after H pylori eradication were classified as H pyloridependent; others were classified as H pylori-independent. The infiltration of NK cells and the expression of CD86 in pre-treatment paraffin-embedded lymphoma tissues were determined by immunohistochemistry. RESULTS:There were 16 H pylori-dependent and 10 H pylori-independent cases. CD86 expression was detected in 11 (68.8%) of 16 H pylori-dependent cases but in none of 10 H pylori-independent cases (P = 0.001). H pylori-dependent high-grade gastric MALT lymphomas contained significantly higher numbers of CD56 (+) NK cells than H pylori-independent cases (2.8±1.4% vs 1.1±0.8%; P = 0.003). CD86 positive MALT lymphomas also showed significantly increased infiltration of CD56 (+) NK cells compared to CD86-negative cases (2.9±1.1% vs 1.4±1.3%; P = 0.005). CONCLUSION:These results suggest that the expression of co-stimulatory marker CD86 and the increased infiltration of NK cells are associated with H pylori-dependent state of early-stage high-grade gastric MALT lymphomas.

Natural Killer (NK) Cells in Antibacterial Innate Immunity: Angels or Devils?

“…Deleterious effects of NK cell activation were reported after infection with both gram-negative (for example, E. coli [185] and Ehrlichia chaffensis [186]) and grampositive bacteria (for example, Streptococcus pneumoniae [187] and Streptococcus pyogenes [188]) independent of the site of infection (systemic, peritoneal or pulmonary). Most interestingly, NK cells may also contribute to adverse evolution of the infectious diseases as shown by their association with a Helicobacter pylori-dependent state of early-stage highgrade gastric mucosa-associated lymphoid tissue lymphoma (189) and Mycobacteria-mediated colitis in susceptible hosts (190). Of course and as expected, NK cells contribute to the deleterious effects seen after LPS injections (85,191).…”

Non-Hodgkin's Lymphoma of Mucosa-Associated Lymphoid Tissue

“…This view was recently challenged by the results of a study in which 10 of 15 patients with stage IE high-grade MALT lymphoma achieved complete histologic remission after anti-H. pylori therapy [105]. In an effort to identify which patients might respond to antibiotic therapy, Kuo et al [106] retrospectively evaluated the expression of CD86 (costimulatory molecule B7.2) and the infiltration by CD56…”

Overexpression of B cell–activating factor of TNF family (BAFF) is associated with Helicobacter pylori–independent growth of gastric diffuse large B-cell lymphoma with histologic evidence of MALT lymphoma

“…The clinicopathologic features of these patients have been previously reported. 2,16 In this study, the diagnosis of DLBCL (MALT) was according to the histologic criteria described by Chan et al 17 and de Jong et al, 18 based on the presence of a diffuse increase of large cells resembling centroblasts or lymphoblasts to between 1% and 10% of the total tumor cells within predominantly low-grade centrocyte-like cell infiltrates (MALT lymphoma predominant), or the predominance of a high-grade large cell lymphoma with only a small residue, low-grade foci, and/or the presence of lymphoepithelial lesions (DLBCL-predominant). Occasional clusters of transformed blast cells or sheets of transformed blast cells (up to 20 cells without the formation of larger sheets) confined within the colonized follicles were considered as an immune response to H pylori stimulation rather than DLBCL (MALT).…”