CXCL12/SDF-1 alpha activates NF-kappaB and promotes oral cancer invasion through the Carma3/Bcl10/Malt1 complex / 国际口腔科学杂志·英文版

<p><b>AIM</b>To determine how SDF-1 alpha/CXCR4 activates nuclear factor-kappa B (NF-kappaB) and promotes oral squamous cell carcinoma (OSCC) invasion.</p><p><b>METHODOLOGY</b>A lentivirus-based knockdown approach was utilized to deplete gene expression. NF-kappaB activation was evaluated by Western blot analysis and electrophoretic mobility shift (EMSA).</p><p><b>RESULTS</b>We show that the activation of NF-kappaB by CXCR4 occurs through the Carma3/Bcl10/Malt1 (CBM) complex in OSCC. We found that loss of components of the CBM complex in HNSCC can inhibit SDF-1 alpha induced phosphorylation and degradation of IkappaBalpha, while TNF alpha induced IKK activation remains unchanged. Further, we identified a role for novel and atypical, but not classical, PKCs in activating IKK through CXCR4. Importantly, inhibition of the CBM complex leads to a significant decrease in SDF-1 alpha mediated invasion of OSCC.</p><p><b>CONCLUSION</b>The CBM complex plays a critical role in CXCR4-induced NF-kappaB activation in OSCC. Targeting molecular components of the NF-kappaB signaling pathway may provide an important therapeutic opportunity in controlling the progression and metastasis of OSCC mediated by SDF-1 alpha.</p>

Abnormal expression of bcl-10 protein in extranodal marginal zone B cell lymphoma of mucosa-associated lymphoid tissue lymphoma type / 中华病理学杂志

<p><b>OBJECTIVE</b>To evaluate the diagnostic role of nuclear expression of bcl-10 protein in extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type.</p><p><b>METHODS</b>One hundred and forty cases of MALT lymphoma were collected from Cancer Hospital of Fudan University (including 38 cases from stomach, 35 cases from ocular adnexa, 16 cases from intestine, 15 cases from skin, 15 cases from salivary gland, 14 cases from lung, 3 cases from thyroid and 4 cases from other sites). Ten cases of reactive follicular hyperplasia of tonsil, 5 cases of reactive lymphoid hyperplasia of orbit and 143 cases of non-Hodgkin's lymphoma other than MALT lymphoma (including 20 cases of NK/T cell lymphoma, 20 cases of follicular lymphomas, 20 cases of anaplastic large cell lymphomas, 20 cases of nodal diffuse large cell B-cell lymphoma (DLBCL), 10 cases of gastric diffuse large B-cell lymphoma, 13 cases of nodal marginal zone B-cell lymphoma, 12 cases of mantle cell lymphoma, 11 cases of splenic marginal zone B-cell lymphoma, 6 cases of angioimmunoblastic T-cell lymphoma, 6 cases of peripheral T-cell lymphoma, not otherwise specified, 3 cases of small lymphocytic lymphoma, 1 case of lymphoplasmacytic lymphoma and 1 case of plasmacytoma were used as controls. Immunohistochemical study for bcl-10, as well as dual staining with CD20, was performed by EnVision method in paraffin sections.</p><p><b>RESULTS</b>In reactive follicular hyperplasia of tonsil, bcl-10 was moderately or strongly expressed in the cytoplasm of germinal center B cells, while the mantle cells were negative and the marginal zone cells and paracortical T cells showed weak staining. In the 5 cases of reactive lymphoid hyperplasia of orbit, 2 were bcl-10-negative and the remaining 3 expressed bcl-10 in the cytoplasm of germinal center B cells. As for non-MALT lymphomas, 3 gastric DLBCL showed nuclear expression. The remaining cases showed variable cytoplasmic staining. In some cases of lymphoma, bcl-10 was expressed in tumor cells but not in reactive lymphoid cells. On the other hand, 92.1% (129/140) of MALT lymphoma were bcl-10 positive. Among those cases, 54.3% (76/140) showed cytoplasmic positivity and 37.9% (53/140) showed nuclear positivity. The nuclear positivity rate of bcl-10 in different anatomic sites was different. The staining was most intense in MALT lymphoma of ocular adnexa. Dual staining with CD20 showed that the bcl-10-positive cells were also CD20-positive, though the number of bcl-10-positive cells were less than that of CD20-positive cells.</p><p><b>CONCLUSIONS</b>Bcl-10 expression in lymphoid hyperplasia is a universal phenomenon. Cytoplasmic expression of bcl-10 is seen in many different kinds of non-Hodgkin's lymphoma and reactive lymphoid conditions. In some cases of lymphoma, bcl-10 is expressed in tumor cells but not in reactive lymphoid cells, suggesting a possible role of abnormal bcl-10 expression in tumorgenesis. Nuclear expression of bcl-10 is seen mainly in MALT lymphoma, especially when occurring in ocular adnexa and lung. This is in contrast to loss of bcl-10 expression in residual germinal center cells.</p>

Clonal relationship between transformed and non-transformed components in mucosa-associated lymphoid tissue lymphoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To analyze the clonal relationship between transformed and non-transformed components in mucosa-associated lymphoid tissue (MALT) lymphoma.</p><p><b>METHODS</b>Six cases of MALT lymphoma with high-grade transformation were studied. Immunohistochemical study was carried out by EliVision using bcl-10 antibody. Reverse transcription-polymerase chain reaction was used to detect the presence of API2-MALT1 fusion gene transcripts. The target cells were selected by laser microdissection and studied by polymerase chain reaction and sequence analysis for rearrangement of immunoglobulin heavy chain gene.</p><p><b>RESULTS</b>In the 6 cases of MALT lymphoma with high-grade transformation, nuclear and cytoplasmic expression of bcl-10 was demonstrated in 1 case, while API2-MALT1 fusion gene was present in 2 cases. Identical fragments of rearranged immunoglobulin heavy chain gene were detected in both transformed and non-transformed components in each of the 6 cases, except for the differences at 2 nucleotide positions in N or D regions in 2 cases.</p><p><b>CONCLUSION</b>The tumor cells from both transformed and non-transformed components in MALT lymphoma derive from the same clone.</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>

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>

Expression of t(11;18) and bcl-10 in gastrointestinal MALT lymphoma / 中国实验血液学杂志

To detect chromosome translocation t(11;18) (q21;q21) and the nuclear expression of bcl-10 in gastrointestinal mucosa-associated lymphoid tissue (MALT) lymphoma in Chinese, a possible API2-MALT fusion transcript specific to t(11; 18) (q21; q21) in tumors from 42 cases of primary gastrointestinal lymphoma (29 cases of low grade MALT lymphoma, 13 cases of transformed MALT lymphoma) and 40 cases of diffuse large B cell lymphoma was examined by means of RT-PCR and proved by DNA-sequencing. Bcl-10 expression was examined by immunohistochemical method. The results showed that t(11;18) (q21;q21) was 14% positive in cases of low grade MALT lymphomas and 46% positive in transformed MALT lymphomas, but none in cases of DLBCL. Bcl-10 nuclear expression was seen 61% in low grade MALT and 69% in transformed MALT lymphoma. It was suggested that t(11;18) (q21;q21) was related to the prognosis and development of highly advanced MALT lymphoma but not relevant to DLBCL. Bcl-10 nuclear expressions were not significantly different between these two groups, which remains to be explained.

Expression of BCL-10 in gastrointestinal mucosa-associated lymphoid tissue lymphoma / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the significance of BCL-10 protein expression in the gastrointestinal mucosa-associated lymphoid tissue (MALT) lymphoma.</p><p><b>METHODS</b>Immunohistochemistry studies were performed using CD20, CD79a, CD3, CD45RO, CD23, CD5, CD10 monoclonal antibodies in 43 cases of gastrointestinal MALT lymphomas, including 25 indolent classical MALT lymphomas and 18 MALT lymphomas with large cell transformation. BCL-10 protein expression was assayed in the tumor cells.</p><p><b>RESULTS</b>In 25 low-grade MALT lymphomas, expression of BCL-10 was found in the nuclei in 10 cases, in both nuclei and cytoplasm 1 case, in cytoplasm 3 cases and no expression 11 cases. In 18 transformed MALT lymphomas, BCL-10 was expressed in the nuclei in 7 cases, in both nuclei and cytoplasm 1 case, in cytoplasm 2 cases, no expression 8 cases. The frequency of BCL-10 expression in nuclei was the highest (44.2%).</p><p><b>CONCLUSION</b>The frequency of BCL-10 expression in nuclei in the gastrointestinal MALT lymphoma is high, indicating that it may associate with the pathogenesis of this entity, and may be helpful to its diagnosis.</p>