TY - JOUR
T1 - MALT lymphoma with t(14;18)(q32;q21)/IGH-MALT1 is characterized by strong cytoplasmic MALT1 and BCL10 expression
AU - Ye, Hongtao
AU - Gong, Liping
AU - Liu, Hongxiang
AU - Hamoudi, Rifat A.
AU - Shirali, Sima
AU - Ho, Liza
AU - Chott, Andreas
AU - Streubel, Berthold
AU - Siebert, Reiner
AU - Gesk, Stefan
AU - Martin-Subero, Jose I.
AU - Radford, John A.
AU - Banerjee, Sankar
AU - Nicholson, Andrew G.
AU - Ranaldi, Renzo
AU - Remstein, Ellen D.
AU - Gao, Zifen
AU - Zheng, Jie
AU - Isaacson, Peter G.
AU - Dogan, Ahmet
AU - Du, Ming Qing
PY - 2005/2
Y1 - 2005/2
N2 - 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 NFκB 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).
AB - 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 NFκB 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).
KW - Bcl10
KW - MALT lymphoma
KW - MALT1
KW - Molecular cytogenetics
KW - Translocation
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U2 - 10.1002/path.1715
DO - 10.1002/path.1715
M3 - Article
C2 - 15682443
AN - SCOPUS:13844266269
SN - 0022-3417
VL - 205
SP - 293
EP - 301
JO - Journal of Pathology
JF - Journal of Pathology
IS - 3
ER -