| [Background and Objective] The pathogenesis of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is a multistage process, but the definite mechanism is still unknown. Several immunological and genetic factors could be enrolled in the development of MALT lymphoma, in which BCL-10 protein nuclear expression and API2-MALT1 fusion transcripts play critical roles. In the present study 86 cases of MALT lymphoma were analyzed according to their clinicopathologic features, immunophenotype and the relationship of BCL-10 protein nuclear expression and API2-MALT1 fusion transcripts in order to investigate their significance in the diagnosis and prognosis of MALT lymphoma. The expression of NFκB in MALT lymphomas was also observed toinvestigate the influence of BCL-10 protein and API2-MALT1 fusion gene on NFκB pathway.[Materials and Methods] 86 cases of MALT lymphoma were selected from Department of Pathology, West China Hospital, Sichuan University between 1990 and 2004. 10 cases of Hashimoto thyroiditis were used as control. All specimens were analyzed by immunohistochemical staining for CD20, CD45RO, CDS, CD 10, BCL-2, immunoglobulin light chain (κ and λ), NFκB, BCL-10, cyclin D1 and Ki-67. RT-PCR was used to detect the transcripts of API2-MALT1 fusion gene. All patients were followed up and divided into two groups according to the patterns of BCL-10 expression for clinicopathologic features study and survival analysis.[Results] 1. The frequency of morphologic plasmacytic differentiation was higher in the cases from thyroid and bowel than those from stomach and lung (P=0.01). Immunohistochemically, the neoplastic lymphoid cells of all 86 cases were positive for CD20 and negative for CD45RO and CD10. The restrictive expression of immunoglobulin light chain was observed in 71 of 86 cases (82. 6%). The BCL-2 protein expression in neoplastic lymphoid cells was found in 32 of 86 cases (37.2%). CD5 expression was observed only in 5 cases (5.8%) which were negative for cyclin Dl. The average Ki-67 proliferation index was 20% in all 86 cases. NFκB expression in both nucleus and cytoplasm was found in 38 of 86 cases (44.2%). In all 10cases of Hashimoto thyroiditis only cytoplasmic BCL-10 expression in lymphoid cells was observed. In 84 of 86 (97.7%) MALT lymphoma cases nuclear and/or cytoplasmic BCL-10 expressions were seen, in which 42 of 86 (48.8%) MALT lymphoma cases exhibited BCL-10 expression in both nucleus and cytoplasm, whereas in other 42 of 86 (48.8%) cases there was only cytoplasmic BCL-10 expression. API2-MALT1 fusion gene was detected in 35 of 86 cases (40.7%) of MALT lymphoma. The variant of transcripts of API2-MALT1 fusion gene, A1446-M1123 (22/35, 62.9%), was detected more frequently than A1446-M814 (13/35, 37.1%) (p=0.011). The frequency of the transcripts of API2-MALT1 fusion gene was lower in the MALT lymphoma in thyroid gland (5.3%) than those in the lung (54.5%), stomach (50.0%) and bowel (50.0%) (p=0.012).Follow-up data were obtained in 70/86 cases (81.4%), with a 5-year survival rate of 83.5%. Clinical stage, gender, age, involved anatomic sites, morphology of tumor cells, the involvement of lymph node, BCL-2 expression and Ki-67 proliferation index were not correlated with the prognosis (P > 0.05).2. The average age (52.8y) of cases with BCL-10 nuclear expression consisting of 23 males and 19 females was 5.7 years younger than that (58.5y) of cases without BCL-10 nuclear expression consisting of 17 males and 27 females. The frequency of BCL-10 nuclear expression was lower in the cases from thyroid gland than those from lung, stomach and bowel (P=0.004). There were no statistic differences in different clinical stage, the morphology of tumor cells,Ki-67 proliferative index and the involvement of lymph node between the groups with and without BCL-10 nuclear expression (P>0.05). Of the 53 gastrointestinal MALT lymphomas, a lower frequency of BCL-10 nuclear expression was observed in cases that tumor confined to within the serosa than in cases that tumor disseminated beyond the serosa (P=0.035). BCL-10 nuclear expression was correlated with API2-MALT1 fusion gene transcript (r=0.374, P=0.000). Furthermore, BCL-10 nuclear expression and API2-MALT1 fusion gene were both correlated with NFkB nuclear expression (r=0.302, P = 0.005 ; r=0.454, P = 0.000, respectively). The statistical difference in survival curves between BCL-10 nuclear positive group and nuclear negative group was not observed (P=0.1247). The prognosis was not correlated with the situation in which BCL-10 nuclear expression, NFkB nuclear expression and API2-MALT1 fusion gene transcript were found simultaneously, either with other situations that any two of them were found (P > 0.05).[Conclusion] 1. The frequency of morphologic plasmacytic differentiation is higher in the cases from thyroid gland and bowel than those from stomach and lung. 2. Clinical stage, gender, age, anatomic sites, morphology of tumor cells, the involvement of lymph node, BCL-2 expression and Ki-67 proliferation index are not correlated with the prognosis. 3. BCL-10 protein may express either both in nucleus and cytoplasm or only in cytoplasm, of which the former is more important in the pathogenesis of MALT lymphoma. BCL-10nuclear expression is correlated with involved anatomic sites (higher in lung and gastrointestinal tract, lower in thyroid gland) and advanced stages. BCL-10 nuclear expression shows few effects on Ki-67 proliferative index, morphology of tumor cells and the prognosis. 4. BCL-10 nuclear expression is correlated with API2-MALT1 fusion gene expression. 5. BCL-10 nuclear expression and API2-MALT1 fusion gene transcript are both correlated with NF/cB nuclear expression. The activation of NF/cB is the common signal transduction pathway of BCL-10 protein and API2-MALT1 fusion gene expression.
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