Correlation between the expressions of CARMA1 gene and MUM1 and its significance in diffuse large B cell lymphoma / 中华血液学杂志

<p><b>OBJECTIVE</b>To determine the correlation between the expression of CARMA1 mRNA and MUM1 protein, as well as its effects on clinicopathological features and prognosis of diffuse large B cell lymphoma (DLBCL).</p><p><b>METHODS</b>The immunophenotype (CD20, CD79a, CD10, MUM1, Bcl6) and proliferation index of DLBCL cells were examined by immunohistochemistry (IHC). CARMA1 mRNA was detected by RT-PCR.</p><p><b>RESULTS</b>CARMA1 mRNA was detected in 76 of 89 (85.40%) cases with DLBCL. The level of CARMA1 mRNA was higher in MUM1-postive group than in MUM1-negative group. No correlation was found in the expression intensity between the two molecules (P = 0.084). Ki67 positive rate was higher in MUM1(+) cases than in MUM1(-) ones (P = 0.030). There was no difference between MUM1(+) and MUM1(-) cases in sex, median age, staging, primary site and other clinicopathological features. In 58 CARMA1 mRNA positive cases, low expression cases showed more in earlier stage and more males. No difference in survival status was identified between cases with and without MUM1 expression, over- and low-expression of CARMA1 mRNA, as well as over- and low-expression of CARMA1 mRNA among 58 cases with MUM1 expression.</p><p><b>CONCLUSION</b>The expression of CARMA1 mRNA is likely associated with the expression of MUM1 and shows male predominance in DLBCL. The expression of CARMA1 may be involved with pathogenesis and progression of ABC-like DLBCL. The two molecules correlated somewhat with some clinicopathological features, but not with survival of DLBCL.</p>

Expression of BCL-10 protein and the relationship with API2-MALT1 fusion gene in extranodal marginal zone B-cell lymphoma of mucosa associated lymphoid tissue / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the relationship of BCL-10 protein and API2-MALT1 fusion gene in MALT lymphoma.</p><p><b>METHODS</b>Specimens from 86 cases of MALT lymphoma were studied by immunohistochemical staining for BCL-10. RT-PCR was used to detect the transcripts of API2-MALT1 fusion gene.</p><p><b>RESULTS</b>In all 10 cases of Hashimoto thyroiditis only cytoplasmic BCL-10 expression in lymphoid cells was observed. In 86 MALT lymphoma cases, 42 cases (48. 8%) exhibited BCL-10 expression in both nucleus and cytoplasm. API2-MALT1 fusion gene was detected in 35 cases (40. 7%) of MALT lymphoma. BCL-10 nuclear expression was correlated with API2-MALT1 fusion gene transcript (r = 0. 374,P = 0. 000).</p><p><b>CONCLUSION</b>BCL-10 nuclear expression is correlated with API2-MALT1 fusion gene expression in MALT lymphoma.</p>

Detection of API2-MALT1 fusion gene in extranodal B-cell lymphoma and its significance / 中华病理学杂志

<p><b>OBJECTIVE</b>To study the expression of API2-MALT1 mRNA in mucosa-associated lymphoid tissue (MALT) lymphoma, extranodal diffuse large B-cell lymphoma (DLBCL) and Hashimoto's thyroiditis, to investigate the expression pattern of API2-MALT1 variants, and to correlate the findings with the clinicopathologic features and prognosis.</p><p><b>METHODS</b>Sixty-two cases of MALT lymphoma (10 from lung, 31 from stomach, 9 from intestine and 12 from thyroid), 32 cases of extranodal DLBCL (16 from stomach, 13 from intestine and 3 from thyroid), 8 cases of Hashimoto's thyroiditis and 5 cases of reactive lymph nodes hyperplasia as negative controls were collected. The expression of API2-MALT1 mRNA was studied in all cases by reverse transcriptase (RT)-polymerase chain reaction (PCR) and nested PCR. The 94 cases of lymphoma were subdivided into API2-MALT1-positive and API2-MALT1-negative groups. Among the patients, 78 were followed up for 6 to 120 months. The differences in clinicopathologic features and prognosis between the two groups were analyzed.</p><p><b>RESULTS</b>API2-MALT1 transcripts were detected in 39 of the 94 lymphoma cases (with 28 cases being MALT lymphoma and 11 cases being extranodal DLBCL). mRNA expression was not detected in all cases of Hashimoto's thyroiditis and the negative controls. Two fusion gene variants, A1446-M1123 and A1446-M814 were found, and A1446-M1123 expression was more common. As for MALT lymphoma cases, the frequency of the fusion gene expression was lower in thyroid, when compared with that in lung, stomach and intestine. API2-MALT1-positive cases had tumors in an earlier stage with milder infiltration of cancer cells, lower relapse rate, and higher five-year survival rate.</p><p><b>CONCLUSIONS</b>The expression of API2-MALT1 mRNA can be detected in both MALT lymphoma and extranodal DLBCL, but not in Hashimoto's thyroiditis. These cases tend to show a more indolent clinical course and better survival. The frequency of t (11; 18) (q21; q21) correlates with the primary sites of MALT lymphoma. The higher incidence of breakpoint at 1123 bp of MALT1 gene in Chinese people may be due to geographical variation.</p>

The frequency of API2-MALT1 fusion gene variants in MALT lymphoma and its correlation with apoptosis of MALT lymphoma / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the frequency of different variant of API2-MALT1 fusion gene in extranodal marginal zone B-cell lymphoma of mucosa-associated tissue(MALT1) lymphoma and the correlation between API2-MALT1 transcript and apoptosis of MALT lymphoma.</p><p><b>METHODS</b>The API2-MALT1 fusion transcripts were detected in 62 cases of MALT lymphoma by reverse transcription-polymeras chain reaction(RT-PCR) and Nested PCR. Five cases with reactive proliferation of lymph node were in use for negative control, and beta-actin was regarded as internal control; the apoptosis index, mRNA and protein of API2 were assayed in all samples by means of TUNEL, RT-PCR and immunohistochemistry respectively.</p><p><b>RESULTS</b>API2-MALT1 transcript was detected in 28 of 62 cases with MALT lymphoma (45.16%). Two kinds of API2-MALT1 variants (A1446-M1123 and A1446-M814) were detected. Variant A1446-M1123 was detected more frequently as compared with A1446-M814. The frequency of API2-MALT1 transcript was lower in thyroid MALT lymphoma(1/12) but similar in pulmonary and gastrointestinal MALT lymphoma. In the group of API2-MALT1(+), the apoptosis index was higher and the API2 mRNA and protein were lower when compared against those in the group of API2MALT1(-). But no significant differences in the levels of apoptosis and API2 were observed between the group of A1446-M1123(+) and A1446-M814(+).</p><p><b>CONCLUSION</b>API2-MALT1 transcript displayed variable frequency in MALT lymphomas of different sites. A1446-M1123 was noted to be probably the main type of API2-MALT1 variant in MALT lymphoma of Chinese. API2-MALT1 transcript was confirmed to be associated with the levels of apoptosis and API2 of MALT lymphoma.</p>

Expression of bcl-10 protein in MALT lymphoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the significance of bcl-10 protein expression in extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma.</p><p><b>METHODS</b>Sixty-two cases of MALT lymphoma were reviewed and immunohistochemical studies for bcl-10 and Ki-67 were performed.</p><p><b>RESULTS</b>Sixty out of the 62 cases studied (96.8%) were positive for bcl-10. Thirty-three (53.2%) showed bcl-10 expression in both the nuclei and cytoplasm, while 27 cases (43.6%) showed only cytoplasmic staining. The 10 cases with Hashimoto's thyroiditis demonstrated bcl-10 expression in the cytoplasm. The mean age of patients with bcl-10 nuclear expression (51.4 years old) was 5.2 years younger than those (56.6 years) without bcl-10 nuclear expression. The former category also showed a male predilection (male to female ratio = 19:14, in contrast to 10:19 in the latter category). The frequency of bcl-10 nuclear expression was lower in cases from thyroid but higher in cases from lung, stomach and intestine (P < 0.05). There was no statistically significant correlation between bcl-10 nuclear expression and clinical tumor stage (P > 0.05) or tumor cell morphology (P > 0.05). Amongst the 40 cases of gastrointestinal MALT lymphoma, bcl-10 nuclear expression correlated with extent of tumor involvement. The protein was expressed in 36.4% (4 out of 11 cases) of MALT lymphoma confined to mucosa or submucosa, 65.2% (15 out of 23 cases) of those invading down to muscularis propria or subserosa, and 100% (all 6 cases) of those extending beyond serosa (P < 0.05). There was no statistically significant difference in Ki-67 proliferative index between bcl-10-positive and bcl-10-negative groups (P < 0.05). Follow-up data were available in 52 patients (83.9%) and the five-year survival rate was no statistically significant difference in survival between bcl-10-positive (29 patients, 96.3%) and bcl-10-negative groups (23 patients, 66.4%, P > 0.05).</p><p><b>CONCLUSIONS</b>Two expression patterns of bcl-10 protein were observed in MALT lymphoma: mixed nuclear-cytoplasmic and cytoplasmic only. The bcl-10 nuclear expression appears more important and correlates with anatomic site of tumor and extent of tumor involvement. Immunohistochemical detection of bcl-10 may carry some diagnostic and prognostic implications in assessment of MALT lymphoma.</p>

Detection of ALK gene translocation by fluorescence in situ hybridization in paraffin-embedded anaplastic large cell lymphoma tissue and its significance / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To compare the value of fluorescence in situ hybridization(FISH) with that of immunohistochemistry in detecting ALK gene translocations and ALK fusion protein in anaplastic large cell lymphoma (ALCL) and investigate the possibility of FISH working on paraffin-embedded ALCL tissue.</p><p><b>METHODS</b>Dual-color FISH and ALK-1 immunohistochemistry were used to detect ALK gene translocation and ALK fusion protein in 22 paraffin-embedded ALCL cases.</p><p><b>RESULTS</b>The digestion time of tissue section was a key-point in the operating of FISH in paraffin-embedded tissue. ALK fusion protein expression was detected with ALK-1 antibody in 12 of the 20 systemic ALCL; it was not detected in 2 primary cutaneous ALCL. The Dual-color FISH results were 100% consonant with the immunohistochemical results.</p><p><b>CONCLUSION</b>(1) Generally, immunohistochemical method is the first choice in detecting ALK gene translocation, but when conditions permit, FISH can be the first choice. (2) By the optimization of experimental conditions, FISH can be successfully performed on paraffin-embedded tissue.</p>

Detection of API2-MALT1 fusion gene transcript and its diagnostic value in pulmonary MALT lymphoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the feasibility of detecting API2-MALT1 fusion gene transcript in paraffin-embedded tissue and its diagnostic value for pulmonary MALT lymphoma.</p><p><b>METHODS</b>Ten archival cases of pulmonary MALT lymphoma were selected and reviewed. Five archival cases of chronic lymphadenitis were used as negative control. Detection of the API2-MALT1 fusion transcript was performed by RT-PCR followed by second-round PCR using nested primers. beta-actin mRNA assay was utilized as an internal control in all samples.</p><p><b>RESULT</b>beta-actin was detected in all samples (100%). The API2-MALT1 fusion transcript was found in 3 of 10 pulmonary MALT lymphomas (30%) and in none of the 5 chronic lymphadenitis cases. The pulmonary lesions in the fusion gene positive cases were all single tumors of less than 5.0 cm in diameter and limited to either the right or left of the lung.</p><p><b>CONCLUSION</b>Detection of API2-MALT1 fusion transcript in paraffin-embedded tissues is feasible by nested RT-PCR and is of diagnostic value. The presence of API2-MALT1 fusion gene may be correlated with a subset of pulmonary MALT lymphomas that have limited lung involvement.</p>