MALT lymphoma with t(14;18)(q32;q21)/IGH‐MALT1 is characterized by strong cytoplasmic MALT1 and BCL10 expression

Abstract

Mucosa-associated lymphoid tissue (MALT) lymphoma is specifically associated with t(11;18)(q21;q21), t(1;14)(p22;q32) and t(14;18)(q32;q21). t(11;18)(q21;q21) fuses the N-terminus of the API2 gene to the C-terminus of the MALT1 gene and generates a functional API2-MALT1 product. t(1;14)(p22;q32) and t(14;18)(q32;q21) bring the BCL10 and MALT1 genes respectively to the IGH locus and deregulate their expression. The oncogenic activity of the three chromosomal translocations is linked by the physiological role of BCL10 and MALT1 in antigen receptor-mediated NFkappaB activation. In this study, MALT1 and BCL10 expression was examined in normal lymphoid tissues and 423 cases of MALT lymphoma from eight sites, and their expression was correlated with the above translocations, which were detected by molecular and molecular cytogenetic methods. In normal B-cell follicles, both MALT1 and BCL10 were expressed predominantly in the cytoplasm, high in centroblasts, moderate in centrocytes and weak/negative in mantle zone B-cells. In MALT lymphoma, MALT1 and BCL10 expression varied among cases with different chromosomal translocations. In 9/9 MALT lymphomas with t(14;18)(q32;q21), tumour cells showed strong homogeneous cytoplasmic expression of both MALT1 and BCL10. In 12/12 cases with evidence of t(1;14)(p22;q32) or variants, tumour cells expressed MALT1 weakly in the cytoplasm but BCL10 strongly in the nuclei. In all 67 MALT lymphomas with t(11;18)(q21;q21), tumour cells expressed weak cytoplasmic MALT1 and moderate nuclear BCL10. In MALT lymphomas without the above translocations, both MALT1 and BCL10, in general, were expressed weakly in the cytoplasm. Real-time quantitative RT-PCR showed a good correlation between MALT1 and BCL10 mRNA expression and underlining genetic changes, with t(14;18)(q32;q21)- and t(1;14)(p22;q32)-positive cases displaying the highest MALT1 and BCL10 mRNA expression respectively. These results show that MALT1 expression pattern is identical to that of BCL10 in normal lymphoid tissues but varies in MALT lymphomas, with high cytoplasmic expression of both MALT1 and BCL10 characterizing those with t(14;18)(q32;q21).

Nuclear bcl10 expression characterizes a group of ocular adnexa MALT lymphomas with shorter failure-free survival

“…7,[27][28][29][30] In MALT lymphoma, deregulation of the expression of MALT1 gene due to chromosomal translocations t(11;18)(q21; q21) and t(14;18)(q32;q21) seems to be one of the main pathogenic mechanisms leading to reduced apoptotic activity. 12,15,22,[31][32][33] In contrast to what has been described in gastric MALT lymphomas, our results did not indicate the presence of t (11;18). This translocation has been extensively examined in gastric MALT lymphomas and is associated with cases of a more advanced stage or those lacking responses to Helicobacter pylori eradication.…”

“…12,15,[31][32][33]35 The nuclear expression of bcl10 has been proposed as a surrogate of NF-kB activation after (11;18)(q21;q21), t(1;14)(p22;q32), while strong cytoplasmic expression has been linked with t(14;18)(q32;q21). 7,12,22,35,36 Strikingly, our data show a clear association between nuclear bcl10, increased expression of p-IkBa, and shorter time to failure. This, in addition to providing predictor parameters, suggests tentative therapeutic targets.…”

“…15,34 It occurs in 20-50% of gastric MALT lymphomas but the true incidence at other sites, with the exception of lung, is largely unknown. 22,24,31,33,34 In particular, the t(11;18) is reported as occurring in MALT lymphomas arising in the ocular adnexa at frequencies between 2.7 and 20%. 10,33,34 The different incidence of this and other translocations in MALT lymphomas from distinct anatomical sites is probably linked to specific prelymphomatous conditions that lead to neoplastic transformation.…”

“…22 Nuclear positivity was also recorded. Phosphorylated IkBa (p-IkBa), considered to be an indirect expression of NF-kB activity, was considered positive when expressed in the cytoplasm and the nucleus.…”

T(14;18)(q32;q21) involving MALT1 and IGH genes occurs in extranodal diffuse large B-cell lymphomas of the breast and testis

“…12 We did not find any structural aberrations in the thyroid lymphomas in our series. Other studies have confirmed the absence of t(14;18)(q32;q21) in thyroid lymphomas, 13,16,27,41 however, t(11;18) and t(3;14) have been reported in extranodal marginal zone lymphoma of the thyroid. 14,26,32,38 Several studies have confirmed differences in prevalence of extranodal marginal zone lymphoma-associated translocations at various anatomic sites and suggest that distinct molecular pathways are involved in the pathogenesis of extranodal marginal zone lymphoma.…”