The study of signal pathway has become a hotspot and a key in life science. In recent years, it has been found that many signaling pathways are associated with the occurrence, development, prognosis and drug resistance of many malignancies, including non-Hodgkin's lymphoma (NHL). Understanding the biological function of the signaling pathway and its relation with NHL, selectively controlling its biological activities may provide a new way for the treatment of NHL. In order to further investigate the function of signal pathways in pathogenesis, development and treatment of NHL, this review summarizes briefly the advances in the signal pathways related with the NHL including NF-κB, PI3K-AKT, Notch, Hh, MAPK, JAK-STAT, Wnt and cAMP.
Humans ; Lymphoma, Non-Hodgkin ; metabolism ; Signal Transduction

To determine whether the p53 expression might be a predictor for treatment sponse and overall survival in nodal non-Hodgkin's lymphoma (NHL), we analyzed e expression of p53 in 69 NHL patients. p53 protein expression was analyzed by munohistochemistry with long-term follow up (1-148 months: median 12.2). p53 pression was noted in 23/69 (33.3%) patients. Complete response (CR) rate to stemic chemotherapy was correlated with stage (I/II) (p=0.038), but not with 3 expression (p=0.2856). Poor overall survival was associated with stage =0.0010) or IPI score (p=0.0076), but not with p53 expression (p=0.8601). From ratification analysis by stage, in stage III/IV patients, the p53 positive oup had a trend to be associated with poor overall survival than the p53 gative group. Multivariate analysis revealed that p53 positive group was sociated with less CR rate compared to the p53 negative group (p=0.046), ereas overall survival was correlated with stage (p=0.0320), not with p53 atus. p53 expression was associated with less CR rate in patients with DLBL. rther studies with large numbers of samples and homogenous group of NHL are eded to determine the prognostic value of cell cycle regulator, p53 in NHL.
Antibodies, Monoclonal ; Cell Cycle Proteins/biosynthesis ; Female ; Gene Expression ; Human ; Immunohistochemistry ; Immunophenotyping ; Lymph Nodes/pathology* ; Lymph Nodes/metabolism* ; Lymphoma, Non-Hodgkin/pathology* ; Lymphoma, Non-Hodgkin/metabolism* ; Lymphoma, Non-Hodgkin/genetics ; Lymphoma, Non-Hodgkin/drug therapy ; Male ; Middle Age/Mpartment of Microbiology ; Prognosis ; Protein p53/immunology ; Protein p53/genetics ; Protein p53/biosynthesis*

The aim of this study was to clarify the clinical significance of CD37 expression in B cells from B acute lymphoblastic leukemia (B-ALL) and B cell non-Hodgkin's lymphoma (B-NHL). The expression level of CD37 on B cells from bone marrow samples of normal controls (n = 19), B-ALL patients [including untreated cases (n = 5) and cases with minimal residual disease (MRD, n = 15)] and B-NHL patients (n = 25) whose bone marrow was involved by lymphoma cells, was detected by multiple parameter flow cytometry. The results indicated that the B cells from both untreated cases and cases with MRD lowly expressed CD37 (1.04 ± 0.24 and 1.50 ± 0.89), the normal precursor B cells (control cases) also lowly expressed CD37 (1.64 ± 0.52). There was no difference of CD37 expression level between 3 groups of cases(P > 0.05). Meanwhile the normal mature B cells and B-NHL cells highly expressed CD37 (14.23 ± 7.84 and 14.53 ± 10.93), but there was no difference of CD37 expression between them (P > 0.05). The comparison of CD37 expression level in normal B cells of development stages showed that the progenitor B cells lowly expressed CD37 (0.88 ± 0.17), the CD37 expression of precursor B cells was enhanced (2.44 ± 0.69), while the CD37 expression level of mature B cells was highest. It is concluded that the low expression of CD37 is not the characteristic of B- ALL cells. The expression level of CD37 increases gradually during the mature process of B cells, i.e, the expression level of CD37 does not associate with benignity or malignancy of B cells.
Antigens, Neoplasm ; metabolism ; Bone Marrow Cells ; metabolism ; Case-Control Studies ; Flow Cytometry ; Humans ; Lymphoma, B-Cell ; metabolism ; pathology ; Lymphoma, Non-Hodgkin ; metabolism ; pathology ; Tetraspanins ; metabolism

To verify the spectrum of CD99-expressing lymphoid malignancy, an immunohistochemical study for CD99 was carried out in 182 cases of non-Hodgkin's lymphoma, including 21 lymphoblastic lymphomas, 11 small lymphocytic lymphomas, 9 mantle cell lymphomas, 12 follicular lymphomas, 37 diffuse large B cell lymphomas, 18 Burkitt's lymphomas, 28 NK/T-cell lymphomas, 8 angioimmunoblastic T-cell lymphomas, 23 peripheral T-cell lymphomas, unspecified, and 15 systemic anaplastic large cell lymphomas. CD99 was positive in all T-lymphoblastic lymphomas and in 60% of B-lymphoblastic lymphomas. Majority of T and NK cell lymphomas were negative for CD99, except anaplastic large cell lymphomas (ALCLs). Eight of 15 cases (54%) of ALCLs reacted with anti CD99 antibody. Seven of 10 (70%) ALK positive ALCLs expressed CD99, whereas only 1 of 5 (20%) ALK negative ALCLs were positive. Of the mature B-cell lymphomas, 5.4% (2/37) of diffuse large B cell lymphomas and 11.1% (2/18) of Burkitt's lymphomas expressed CD99. In conclusion, CD99 is infrequently expressed in mature B and T cell lymphomas, except ALK-positive ALCL. High expression of CD99 in ALK-positive ALCL is unexpected finding and its biologic and clinical significances have yet to be clarified.
Antigens, CD/*metabolism ; Blotting, Western ; Cell Adhesion Molecules/*metabolism ; Humans ; Immunohistochemistry ; Lymphoma, Large-Cell/enzymology/*immunology/pathology ; Lymphoma, Non-Hodgkin/enzymology/*immunology/pathology ; Protein-Tyrosine Kinase/immunology/*metabolism

This study was aimed to investigate the relationship of Ki-67 proliferation index (Ki-67 PI) with non-Hodgkin's lymphoma(NHL) typing and biological behavior, as well as its significance in clinical characters and prognosis of diffuse large B-cell lymphoma(DLBCL). A total of 542 cases of NHL in our hospital from 1st January 2001 to 31st December 2010 were retrospectively analyzed, and Ki-67 PI was all assayed immunohistochemically, and a total of 82 cases of newly-diagnosed DLBCL with more clinical records were investigated. The results indicated that according to the World Health Organization (WHO) histopathological classification of lymphoma, Ki-67 PI was different as classification for NHL subgroups was different. The Ki-67 PI increased with aggressive progression of NHL. The mean Ki-67 PI ranged from 25.5% in indolent lymphoma to 98.4% in very aggressive lymphoma. ROC curve analysis demonstrated that the 50% was the cut-off value distinguishing indolent from aggressive disease. On ROC curve analysis, Ki-67 PI of 75% was found to significantly discriminate patients with DLBCL who had a good or bad prognosis. There was a significant correlation of Ki-67 PI with Ann Arbor stage and LDH level. When the DLBCL cases were divided by Ann Arbor stage and IPI score, the 3-year overall survival (OS) of patients with a low Ki-67 PI (≤ 75%) in the group of Ann Arbor stage III-IV and high LDH level was higher than those with a high Ki-67 PI (> 75%) among the patients with B symptoms and IPI 3.0-5. 3-year OS in those with a low Ki-67 PI (≤ 75%) in the group of Ann Arbor stage III-IV and normal LDH level was higher than those with a high Ki-67 PI (> 75%) among the patients with B symptoms. 3-year OS of patients with a low Ki-67 PI (≤ 75%) in the group at III-IV stage and a high LDH level was higher than those with a high Ki-67 PI (> 75%). It is concluded that a cut-off value of 50% can be helpful to differentiate indolent from aggressive NHL. In DLBCL, a cut-off value of 75% can distinguish patients with a good or bad prognosis when combined with other prognostic factors, i.e. B symptoms, Ann Arbor stage, IPI score and lactate dehydrogenase (LDH) level.
Female ; Humans ; Ki-67 Antigen ; metabolism ; Lymphoma, Large B-Cell, Diffuse ; metabolism ; pathology ; Lymphoma, Non-Hodgkin ; metabolism ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis

OBJECTIVETo investigate the correlation of Epstein-Barr virus (EBV) infection and childhood lymphoma.

METHODSParaffin-embedded specimens of lymphoma collected between 1996 and 2005, including 36 Hodgkin lymphomas (HL) and 51 non-Hodgkin lymphomas (NHL), were included in this study. Paraffin-embedded specimens of reactive hyperplasia of lymph nodes (RL) collected during the same period were used as controls. Immunohistochemical (IHC) assay was used to detect EBV-LMP1 and in situ hybridization (ISH) to detect EBV-EBERs.

RESULTSEBV was detected in 72.2% (26/36) of the Hodgkin lymphomas, 15.7% (8/51) of the non-Hodgkin lymphomas and 33.3% (15/45) of the reactive hyperplasia of lymph nodes. There was a significant difference among Hodgkin lymphoma, non-Hodgkin lymphoma and RL (P = 0. 000).

CONCLUSIONChildhood Hodgkin lymphoma is closely correlated with Epstein-Barr virus infection. However, the low rate of EBV infection detected in childhood non-Hodgkin lymphoma might be due to heterogeneous distribution of pathological types in this study.

Child ; Child, Preschool ; Epstein-Barr Virus Infections ; complications ; metabolism ; Female ; Herpesvirus 4, Human ; isolation & purification ; Hodgkin Disease ; complications ; metabolism ; virology ; Humans ; Lymphoma, Non-Hodgkin ; complications ; metabolism ; virology ; Male ; Pseudolymphoma ; complications ; metabolism ; virology ; RNA, Viral ; metabolism ; Viral Matrix Proteins ; metabolism

OBJECTIVETo investigate the expression of CD147 and matrix metalloproteinase-9 (MMP-9) in children with non-Hodgkin's lymphoma (NHL) and its correlation with clinical stage, tumor size, bone marrow invasion, immunological typing, serum lactate dehydrogenase (LDH) concentration, and prognosis.

METHODSSpecimens excised from NHL patients were prepared. Expression of CD147 and MMP-9 were tested by streptavidin-biotin complex (SABC) immunohistochemistry and its correlation with clinical results were analyzed.

RESULTSThe positive rate of CD147 expression was 73% (45/62), 17 cases were (-), 11 cases (+), 34 cases (++) and 21 cases (+++). The positive rate of MMP-9 expression was 81% (50/62), 12 cases were (-), 13 cases (+), 18 cases (++) and 19 cases (+++). The Spearman rank correlation analysis indicated that there was a positive correlation between CD147 and MMP-9 expressions in NHL (r(S) = 0.763, P = 0.034). Expression of CD147 was determined in relation to factors that included clinical bone marrow invasion, tumor size, LDH level as well as the clinical stage; expression of MMP-9 had a positive correlation with bone marrow invasion, tumor size and clinical phases. The 5-year survival rates (5YSR) were 78% (22/28) and 45% (15/34) in the cases whose CD147 expression was (-)-(+) and (++)-(+++), respectively, and 5YSR were 84% (21/25) and 43% (16/37) in the cases whose MMP-9 expression was (-)-(+) and (++)-(+++) respectively, the difference was significant. Cox multivariate analysis showed that both CD147 and MMP-9 were important prognostic factors.

CONCLUSIONThe increased expression of CD147 and/or MMP-9 correlates with a poor clinical outcome in patients with NHL.

Adolescent ; Basigin ; metabolism ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Lymphoma, Non-Hodgkin ; diagnosis ; metabolism ; pathology ; Male ; Matrix Metalloproteinase 9 ; metabolism ; Prognosis ; Survival Rate

OBJECTIVETo investigate the expression, localization and interrelationship of P27(kip1) and cyclin D3 in non-Hodgkin's lymphoma (NHL).

METHODSThe expressions of P27(kip1), cyclin D3 and index Ki-67 was detected in 100 NHL and 20 reactive lymph nodes by immunohistochemical technique. The expression and localization of P27(kip1) and cyclin D3 in 3 NHL cell lines were detected by Western blot, double immunolabelling and laser scanning confocal microscopy, respectively.

RESULTSIn general the expression of P27(kip1) in NHL was lower than in control group, and was negatively related to the tumor aggressiveness and proliferating activity; the expression of cyclin D3 in NHL was higher than in control group, and was positively related to the tumor aggressiveness and proliferating activity. There was a negative correlation between P27(kip1) and cyclin D3. Nevertheless, anomalous high P27(kip1) expression was found in a few NHL tissues with high expression of cyclin D3 and Ki-67. Overexpression and colocalization of P27(kip1) and cyclin D3 was found in Raji cell line.

CONCLUSIONSUnder expression of P27(kip1) and overexpression of cyclin D3 may play a role in the occurrence and development of NHL. Anomalous high P27(kip1) expression and its interaction with cyclin D3 may be another mechanism for tumor genesis of NHL.

Cell Line, Tumor ; Cyclin D3 ; Cyclin-Dependent Kinase Inhibitor p27 ; genetics ; metabolism ; Cyclins ; genetics ; metabolism ; Humans ; Lymphoma, Non-Hodgkin ; genetics ; metabolism ; pathology

CD56 Antigen ; metabolism ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Killer Cells, Natural ; metabolism ; pathology ; Leukocyte Common Antigens ; metabolism ; Leukosialin ; metabolism ; Lymphoma, Extranodal NK-T-Cell ; metabolism ; pathology ; Lymphoma, Non-Hodgkin ; metabolism ; pathology ; Middle Aged ; Skin Neoplasms ; metabolism ; pathology

The Pax5 gene encodes the B-cell-specific activator protein which is a key regulator in development and differentiation of B-cell. We studied the expression of Pax5 in hematologic malignancies to evaluate the diagnostic utility as a B cell marker. Materials included 70 B cell lymphomas, 26 T cell lymphomas, 53 acute leukemias, and 6 multiple myelomas (MMs). Representative areas from the paraffinembedded tissues were selected for tissue microarray, and the expressions of Pax5 was immunohistochemically evaluated. Pax5 was strongly expressed in most of the B cell lymphomas; 44 of 47 diffuse large B cell lymphomas (93.6%), 15 of 16 marginal zone B cell lymphomas (93.8%), all 3 mantle cell lymphomas, 2 follicular lymphomas, and 2 Burkitt's lymphomas (100%). However, Pax5 was expressed in only one of 26 T cell lymphomas. Among leukemias, it was expressed in 10 of the 14 B acute lymphocytic leukemias (ALLs) (72.4%), but also in 3 of the 6 T ALLs (50%), 13 of the 26 acute myelogenous leukemias (AMLs) (50%) and in all 3 ALL arising in chronic myelogenous leukemias and 4 mixed B ALL and AML. In MMs, Pax5 was negative in all cases. We concluded that Pax5 is very useful B cell marker in classification of lymphomas, but not of acute leukemias.
B-Lymphocytes/pathology/physiology ; DNA-Binding Proteins/genetics/*metabolism ; Human ; Leukemia/classification/*metabolism/pathology ; Lymphoma, Non-Hodgkin/classification/*metabolism/pathology ; Support, Non-U.S. Gov't ; Tonsil/cytology/metabolism/pathology ; Transcription Factors/genetics/*metabolism ; Tumor Markers, Biological/*metabolism