ABSTRACT
Several balanced translocations have been identified in extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) but there are few data regarding their frequency in different anatomic sites or the frequency of translocations involving BCL6 or kappa or lambda immunoglobulin light chain genes (IGK or IGL), particularly in patients from geographic regions other than Europe and Japan. One hundred thirty-three paraffin-embedded North American primary MALT lymphoma specimens from diverse anatomic sites were studied by fluorescence in situ hybridization (FISH) using probes for API2-MALT1, IGH-MALT1, IGH-BCL10, IGH-FOXP1, IGH, +/- centromeres 3, 7, 12, and 18, and a subset (n=74) were analyzed using FISH probes for IGK, IGL, and BCL6. Translocations were mutually exclusive and were detected in 26% of cases (17% API2-MALT1, 5% IGH-MALT1, 3% IGH-unknown translocation partner, and 1% IGH-BCL10). Aneuploidy was associated with IGH-MALT1 and IGH-BCL10 but only rarely with API2-MALT1. There was striking site specificity, with API2-MALT1 showing a marked predilection for lung and intestine, and IGH-MALT1 and IGH-BCL10 occurring almost exclusively in lung. Twenty-three percent of translocation-negative primary MALT lymphomas from diverse sites showed complete/partial trisomy 18. No MALT lymphomas with translocations involving IGK, IGL, BCL6, or FOXP1 were identified. This FISH panel detected cytogenetic abnormalities in half of all MALT lymphomas, and translocations arose preferentially in MALT lymphomas of the lung and gastrointestinal tract. Differences in incidence and anatomic site specificity of translocations between North American and non-North American cases may reflect geographic variability of infectious or other etiologic factors.
Subject(s)
Aneuploidy , Intestinal Neoplasms/genetics , Lung Neoplasms/genetics , Lymphoma, B-Cell, Marginal Zone/genetics , Translocation, Genetic/genetics , Adaptor Proteins, Signal Transducing/genetics , Adaptor Proteins, Signal Transducing/metabolism , B-Cell CLL-Lymphoma 10 Protein , Caspases/genetics , Genetic Markers/genetics , Humans , Immunoglobulin Light Chains/genetics , In Situ Hybridization, Fluorescence , Incidence , Intestinal Neoplasms/pathology , Lung Neoplasms/pathology , Lymphoma, B-Cell, Marginal Zone/immunology , Lymphoma, B-Cell, Marginal Zone/pathology , Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein , Neoplasm Proteins/genetics , North America , Oncogene Proteins, Fusion/genetics , Oncogene Proteins, Fusion/metabolism , Organ Specificity , Tissue Array AnalysisABSTRACT
Detection of t(14;18)(q32;q21)-IgH/bcl-2, which is present in 70% to 95% of follicular lymphomas (FLs), might aid in diagnosing FL. The efficacy of routine polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH) techniques in detecting t(14;18) in paraffin-embedded tissue samples was compared on 5 normal tonsils and 28 FLs demonstrated to be t(14;18)+ by previous karyotyping. There was technical failure in 14 (50%) of the FLs by PCR, likely due to B-5 fixation, and 4 (14%) of FLs by FISH, likely due to advanced specimen age. In the remaining successful cases, 5 (36%) of 14 were positive by PCR and 24 (100%) of 24 were positive by FISH. All 5 normal tonsils were negative by both methods. FISH is superior to PCR for detecting t(14;18) from paraffin-embedded tissue samples because it is more sensitive and equally specific.
