BCL10 Expression in Normal and Neoplastic Lymphoid Tissue

Abstract

BCL10 is an apoptotic regulatory molecule identified through its direct involvement in t(1;14)(p22;q32) of mucosa-associated lymphoid tissue (MALT) lymphoma. We examined BCL10 protein expression in various normal tissues and B-cell lymphomas by immunohistochemistry of formalin-fixed and paraffin-embedded tissues using mouse BCL10 monoclonal antibodies. BCL10 protein was expressed in lymphoid tissue but not in 21 various other tissues with the exception of breast. In normal B-cell follicles, the protein was expressed abundantly in the germinal center B cells, moderately in the marginal zone, but only weakly in the mantle zone B cells. Irrespective of their stage of B-cell maturation, BCL10 was predominantly expressed in the cytoplasm. In contrast, each of the four MALT lymphomas with t(1;14)(p22;q32) showed strong BCL10 expression in both the nucleus and cytoplasm. Twenty of 36 (55%) MALT lymphomas lacking the translocation exhibited BCL10 expression in both the nucleus and cytoplasm although at a much lower level, whereas the remaining 16 cases displayed only cytoplasmic BCL10. Unlike MALT lymphoma, both follicular and mantle cell lymphomas generally displayed BCL10 expression compatible to their normal cell counterparts. Our results show differential expression of BCL10 protein among various B-cell populations of the B-cell follicle, indicating its importance in B-cell maturation. The subcellular localization of BCL10 was frequently altered in MALT lymphoma in comparison with its normal cell counterparts, suggesting that ectopic BCL10 expression may be important in the development of this type of tumor.

t(1;14) and t(11;18) in the differential diagnosis of Waldenström's macroglobulinemia

“…The tumor cells with t(1;14)(p22;q32) are characterized by strong uniformed BCL10 nuclear staining. 10 We previously showed that 5/5 cytogenetically proven t(1;14)(p22;q32) cases displayed strong BCL10 nuclear expression 9 (Du et al, unpublished data). In a recent study, we further confirmed t(1;14)(p22;q32) or its variants in 5/7 cases showing strong BCL10 nuclear expression by interphase FISH.…”

“…BCL10 immunohistochemistry was performed to attempt to identify evidence of t(1;14)(p22;q32) and both bone marrow and gastric biopsies showed strong homogeneous BCL10 nuclear expression in most if not all tumor cells (Figure 1a), similar to that seen in MALT lymphoma with t(1;14)(p22;q32) or its variants. 9,10 To verify whether the tumor cells harbor a BCL10 involved chromosomal translocation, interphase fluorescence in situ hybridization (FISH) was performed. 10 Although various pretreatments were tried, interphase FISH failed due to poor quality of the biopsy.…”

Variable frequencies of MALT lymphoma-associated genetic aberrations in MALT lymphomas of different sites

“…32 In contrast to normal lymphoid cells and to MALT lymphomas negative for the t(1;14)(p22;q32), MALT lymphomas harboring the t(1;14)(p22;q32) typically show high nuclear BCL10 expression. 33 By screening 331 MALT lymphomas immunohistochemically for BCL10 expression, Ye et al identified 12 cases (3.6%) comprising six gastric, five pulmonary, and one cutaneous MALT lymphoma, and confirmed the rearrangement of BCL10 by FISH in five of seven cases tested. 20 Our molecular cytogenetic study revealed BCL10 rearrangement in four of 252 cases (1.6%), two of which occurred in the colorectum and one each in the lung and salivary gland, respectively.…”

Molecular pathogenesis of MALT lymphoma: two signaling pathways underlying the antiapoptotic effect of API2-MALT1 fusion protein

“…78 The BCL10 protein is expressed predominantly in the cytoplasm of germinal center B cells, 79 whereas this protein is found to be strongly expressed in the nucleus of MALT lymphomas with t (1;14). 79 Moderate nuclear expression of BCL10 is also observed in nearly 100% of MALT lymphomas with the other translocation, t(11;18).…”