title: MALT1 gene rearrangements and NF-kappaB activation involving p65 and p50 are absent or rare in primary MALT lymphomas of the breast.
abstract: Mucosa associated lymphoid tissue (MALT) lymphomas arising in the breast are uncommon and few cases have been assessed for MALT lymphoma-associated translocations, BCL-10 expression, or NF-kappaB activation. In this study, we analyzed eight cases of primary breast MALT lymphoma. We also included 14 cases of primary breast diffuse large B-cell lymphoma since some of these may represent transformation of MALT lymphoma, known to occur at extra-mammary MALT sites. All cases were assessed for MALT1 gene rearrangements by fluorescence in situ hybridization (FISH). Using immunohistochemical methods, all cases were assessed for BCL-10, and subsets were assessed for NF-kappaB p65 and p50. None of the cases had MALT1 gene rearrangements by FISH. Of eight MALT lymphomas, BCL-10 was positive in seven (88%), with moderate nuclear and cytoplasmic staining in six, and a weak cytoplasmic staining in one. NF-kappaB p65 (n=8) and p50 (n=5) were negative or showed only cytoplasmic staining (ie inactivated) in all cases. Of 14 diffuse large B-cell lymphoma cases, BCL-10 was positive in 12 (87%), with weak-to-moderate cytoplasmic staining in 10, weak cytoplasmic and focally nuclear staining in one, and a moderate-to-strong nuclear and cytoplasmic staining in one. NF-kappaB p65 (n=11) showed cytoplasmic staining in all cases, whereas p50 (n=8) showed nuclear positivity (ie activated) in two (25%) cases. We conclude that MALT1 gene rearrangements are absent or rare in primary breast MALT lymphoma and diffuse large B-cell lymphoma. In MALT lymphomas, the moderate BCL-10 nuclear expression in six neoplasms is inconsistent with the FISH results, suggesting that BCL-10 immunostaining overestimates the frequency of MALT1 gene rearrangements. We also could not demonstrate NF-kappaB activation using nuclear staining for p65 and p50. In contrast, breast diffuse large B-cell lymphomas are heterogeneous. Weak cytoplasmic BCL-10 staining in most cases and evidence of NF-kappaB p50 activation in a subset differs from breast MALT lymphomas.
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Sameer S
authors.initials: SS
authors.lastname: Talwalkar
authors.forename: Jose R
authors.initials: JR
authors.lastname: Valbuena
authors.forename: Lynne V
authors.initials: LV
authors.lastname: Abruzzo
authors.forename: Joan H
authors.initials: JH
authors.lastname: Admirand
authors.forename: Sergej N
authors.initials: SN
authors.lastname: Konoplev
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Bueso-Ramos
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000074018:B-Cell CLL-Lymphoma 10 Protein; D001943:Breast Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology*; D018567:Breast Neoplasms, Male / Q000235:genetics; D020169:Caspases / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D018442:Lymphoma, B-Cell, Marginal Zone / Q000737:chemistry / Q000235:genetics* / Q000473:pathology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics; D008297:Male; D008875:Middle Aged; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D016328:NF-kappa B / Q000032:analysis*; D052002:NF-kappa B p50 Subunit / Q000032:analysis; D009363:Neoplasm Proteins / Q000235:genetics*; D051996:Transcription Factor RelA / Q000032:analysis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000074018:B-Cell CLL-Lymphoma 10 Protein; C118591:BCL10 protein, human; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D009363:Neoplasm Proteins; D051996:Transcription Factor RelA; D020169:Caspases; C400109:MALT1 protein, human; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein