title: Detection of immunoglobulin heavy chain gene rearrangement by polymerase chain reaction in chronic active gastritis associated with Helicobacter pylori.
abstract: Chronic active gastritis associated with Helicobacter pylori (CAG-Hp) has been linked to the pathogenesis of gastric B-cell lymphomas of mucosa-associated lymphoid tissue (MALT). To determine whether monoclonal lymphoid populations are present in CAG-Hp and histological predictors of monoclonality exist, the authors examined 46 endoscopic biopsies from 41 patients with CAG-Hp. The authors scored gastric biopsies for the presence of lymphoepithelial lesions (LELs), intensity of lymphoid infiltrate, presence of lymphoid aggregates and germinal centers, coexpression of CD43 (Leu 22) on B cells, and cytoplasmic immunoglobulin light chain restriction in formalin-fixed, paraffin embedded tissues. DNA extracts from these routinely processed tissues were analyzed for immunoglobulin heavy chain (IgH) gene rearrangement by polymerase chain reaction (PCR). Histological features, immunophenotype, gene rearrangement status, and clinical information were correlated. Six of the 46 biopsies (13%) from six of 41 patients (15%) showed a monoclonal PCR pattern. Monoclonal PCR patterns correlated with the presence of LELs (P<.015) but not with intensity of lymphoid infiltrate, presence of germinal centers, or presence of lymphoid aggregates. LELs correlated with germinal centers (P<.003) and intensity of infiltrate (P<.0001). None of the cases showed cytoplasmic light chain restriction nor coexpression of CD43 on B cells by immunohistochemistry. Clinical follow-up was available in all six patients whose gastric biopsies had a monoclonal PCR pattern (median, 58 months; range, 1 to 66 months) and 33 of the 35 patients with biopsies showing a polyclonal PCR pattern (median, 41 months; range 0.1 to 63 months). No patient developed gastric lymphoma. Monoclonality of lymphoid cells was detected by IgH PCR in 13% of patients with CAG-Hp. Although the authors cannot exclude the possibility that some patients with monoclonal gastric lymphoid infiltrates may eventually develop overt lymphoma, no histological, immunophenotypic, nor clinical evidence of lymphoma was noted at presentation or on clinical follow-up. Given the high incidence of CAG-Hp in the general population and the relatively low incidence of gastric MALT lymphoma, clinicopathologic correlation is needed when interpreting tests for clonality in this setting. The presence of clonal IgH gene rearrangement in CAG-Hp supports the hypothesis that H pylori is involved in the pathogenesis of low grade gastric B-cell MALT lymphomas.
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, 48109-0602, USA.
authors.forename: E D
authors.initials: ED
authors.lastname: Hsi
authors.forename: J K
authors.initials: JK
authors.lastname: Greenson
authors.forename: T P
authors.initials: TP
authors.lastname: Singleton
authors.forename: J
authors.initials: J
authors.lastname: Siddiqui
authors.forename: B
authors.initials: B
authors.lastname: Schnitzer
authors.forename: C W
authors.initials: CW
authors.lastname: Ross
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D002908:Chronic Disease; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005756:Gastritis / Q000235:genetics* / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D015321:Gene Rearrangement; D016481:Helicobacter Infections / Q000235:genetics* / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D016480:Helicobacter pylori; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods*; D012189:Retrospective Studies; D017422:Sequence Analysis, DNA
chemical_list: D000911:Antibodies, Monoclonal; D007143:Immunoglobulin Heavy Chains