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Translocations Involving the Immunoglobulin Heavy Chain Gene Locus Predict Better Survival in Gastric Diffuse Large B-Cell Lymphoma

Authors' Affiliations: ¹ Division of Molecular Histopathology, Department of Pathology, University of Cambridge, Cambridge, United Kingdom; Departments of ² Medicine and Clinical Science; ³ Anatomic Pathology, Graduate School of Medical Sciences; and ⁴ Department of Pathology, School of Medicine, Fukuoka University, Fukuoka, Japan; ⁵ Nuffield Department of Clinical Laboratory Sciences, University of Oxford, Oxford, United Kingdom; ⁶ Department of Pathology, Medical University of Vienna, Vienna, Austria; ⁷ Department of Histopathology, Ospedale S. Orsola FBF, Brescia, Italy; and GELD Departments of ⁸ Pathology and ⁹ Gastroenterology, AP-HP, Hôpital Saint Antoine, Paris, France

Requests for reprints: Shotaro Nakamura, Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan. Phone: 81-92-642-5261; Fax: 81-92-642-5273; E-mail: shonaka{at}intmed2.med.kyushu-u.ac.jp.

Purpose: The pathogenesis and clinical heterogeneity of gastric diffuse large B-cell lymphoma (DLBCL) are poorly understood. We have comprehensively investigated the incidence and clinical significance of lymphoma-associated chromosomal translocations, particularly those involving the immunoglobulin heavy chain (IGH) gene locus, in a large series of gastric DLBCL.

Experimental Design: One hundred forty-one cases of primary gastric DLBCL [58 with mucosa-associated lymphoid tissue (MALT) lymphoma and 83 without MALT lymphoma] were enrolled. Translocations involving BCL6, c-MYC, FOXP1, MALT1, and IGH were investigated using interphase fluorescence in situ hybridization. In positive cases, additional fluorescence in situ hybridization was done with appropriate probes for potential partner genes. Cases were classified into germinal center B-cell–like (GCB) or non-GCB subgroups by immunophenotyping with CD10, BCL6, and MUM1.

Results: Translocations involving IGH were detected in 36 (32%) of 111 cases; their partner genes included BCL6 (n = 10), c-MYC (n = 5), and FOXP1 (n = 3) but remained unknown in the remaining 18 cases. t(14;18)/IGH-BCL2, t(14;18)/IGH-MALT1, and t(1;14)/BCL10-IGH were not detected in any case. t(11;18)/API2-MALT1 was detected in none of the cases, except for one case of DLBCL with MALT lymphoma, which showed positive signals only in MALT lymphoma cells. IGH-involved translocation was associated with younger age but not with any other clinicopathologic factors including GCB or non-GCB immunophenotypes. Cox multivariate analysis revealed that IGH-involved translocation, in addition to younger age and early stage, was an independent prognostic factor for better overall and EFSs.

Conclusion: IGH-involved translocations are frequent in gastric DLBCL and seem to identify cases with favorable prognosis.