Adenolymphoma ; enzymology ; metabolism ; Humans ; Lymphoma, T-Cell ; enzymology ; metabolism ; Lymphoma, T-Cell, Peripheral ; enzymology ; metabolism ; Male ; Middle Aged ; Nitric Oxide Synthase Type I ; metabolism ; Up-Regulation

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

OBJECTIVETo detect the expression level of asparagine synthetase (ASNS) in patients with relapsed or refractory extranodal NK/T cell lymphoma and explore its clinical significance.

METHODSTen patients with relapsed or refractory extranodal NK/T cell lymphoma admitted in our department from January, 2013 to January, 2016 were analyzed. The diagnoses were confirmed by pathological and immunohistochemical examination following failed chemotherapies in all cases. Branched DNA-liquidchip technique (bDNA-LCT) was used for detecting ASNS mRNA expression in paraffin-embedded tissue sections in the 10 cases of relapsed or refractory extranodal NK/T cell lymphoma and in 5 cases of chronic rhinitis. The correlations were analyzed between ASNS expression and the clinicopathological features and outcomes of the patients with failed chemotherapy regimens containing asparaginasum.

RESULTSSix out of the 10 patients with relapsed or refractory extranodal NK/T cell lymphoma died due to diseaseprogression. The expression level of ASNS was significantly higher in the lymphoma tissues than in tissue specimens of chronic rhinitis (P<0.05). The expression level of ASNS was associated with the International Prognostic Index (P=0.023) in patients with relapsed or refractory extranodal NK/T cell lymphoma, and Kaplan-Meier curve showed that a high ASNS expression was correlated with a reduced overall survival and progression-free survival of the patients.

CONCLUSIONAsparaginasum-based chemotherapy regimens are recommended for treatment of relapsed or refractory extranodal NK/T cell lymphoma with low ASNS expressions.

Aspartate-Ammonia Ligase ; metabolism ; Disease-Free Survival ; Humans ; Lymphoma, Extranodal NK-T-Cell ; enzymology ; Recurrence

Granzyme B is one of the serine proteases expressed in natural killer (NK) cells and activated cytotoxic T-lymphocytes. To evaluate the usefulness of granzyme B immunoreactivity in the diagnosis of T/NK-cell lymphoma, we studied 69 cases of lymphomas occurring in the upper aerodigestive tract by paraffin-section immunohistochemistry using a commercially available monoclonal antibody to granzyme B (GrB-7). All 19 cases of T/NK-cell lymphomas defined by the expression of CD56 (NHK-1) and one or both T-cell markers (polyclonal CD3 and CD45RO) expressed granular cytoplasmic granzyme B immunoreactivity. Two out of 9 cases of T-cell lymphomas showing no CD56 expression demonstrated strong granzyme B immunoreactivity. No tumor cells among 39 cases of B-cell diffuse large cell lymphomas and 2 cases of null cell diffuse large cell lymphomas were immunoreactive for granzyme B, however a few scattered granzyme B-positive reactive small lymphoid cells were consistently observed. Based on its sensitivity in this study as well as its reactivity in routinely processed tissue sections, even without heat-induced epitope retrieval technique, monoclonal antibody to granzyme B (GrB-7) can be applied as a useful marker in the diagnosis of T/NK-cell lymphomas in conjunction with CD56.
Adult ; Aged ; Aged, 80 and over ; Child ; Female ; Human ; Immunohistochemistry ; Killer Cells/pathology* ; Lymphoma/pathology* ; Lymphoma/enzymology* ; Lymphoma, T-Cell/pathology ; Lymphoma, T-Cell/enzymology* ; Male ; Middle Age ; Serine Endopeptidases/metabolism*

Gastric CD30-positive anaplastic large-cell lymphoma is a very rare disease. It is sometimes difficult to distinguish it from undifferentiated carcinoma, sarcoma and so on. We report here on a case of primary gastric anaplastic large-cell lymphoma. A 50-yr-old woman complained of epigastric pain and severe chest pain for 1 week. The gastroendoscopic examination revealed geographic mucosal irregularities with shallow ulceration at the antrum. She underwent a total gastrectomy. The gross finding of the resected stomach was an 8 x 4.5 cm sized ulceroinfiltrative lesion at the pyloric antrum along the lesser curvature. The microscopic examination revealed diffuse and solid proliferations of large atypical cells with pleomorphic nuclei. Immunohistochemically, the tumor cells were positive for CD30, vimentin and CD3, and this was a finding compatible with anaplastic large-cell lymphoma. To the best of our knowledge, this is the first such reported case in Korea.
Antigens, CD30/*metabolism ; Female ; Humans ; Immunohistochemistry ; Korea ; Lymphoma, Large-Cell/enzymology/*immunology/*pathology ; Middle Aged ; Protein-Tyrosine Kinase/metabolism ; Stomach Neoplasms/enzymology/*immunology/*pathology

OBJECTIVETo investigate the expression of PTEN and Caspase-3 in malignant lymphoma of the stomach and explore their role in progression of primary gastric malignant lymphoma.

METHODSFormalin-fixed paraffin embedded tissues from 56 cases of primary gastric malignant lymphoma and their adjacent non-tumor mucosa were evaluated for PTEN and Caspase-3 protein expression by streptavidin-biotin-complex (SABC) immunohistochemistry. Their expression was compared with clinical tumor parameters with the relationship between PTEN and Caspase-3 expression concerned as well.

RESULTSThe positive rate of PTEN expression in primary gastric lymphomas (50.0%, 28/56) was significantly lower than that in adjacent non-tumor gastric mucosa (96.4%, 27/28) (P < 0.05). Meanwhile, 43 of 56 (76.8%) gastric lymphomas indicated Caspase-3 expression, less than that in adjacent non-tumor mucosa (93.5%, 29/31) (P < 0.05). The expression of PTEN was negatively correlated with invasion and lymph node metastasis of gastric lymphoma (P < 0.05), while the Caspase-3 expression was negatively associated with the latter one (P < 0.05). Additionally, the PTEN expression was positively correlated with Caspase-3 expression in the primary gastric malignant lymphoma (P < 0.05).

CONCLUSIONSThe down-regulated expression of PTEN and Caspase-3 played an important role in progression of primary malignant gastric lymphoma. PTEN, as a molecular marker of pathobiological behaviors of tumor, contributes to tumor progression by increasing cell mobility and angiogenesis, as well as decreasing cell adhesion and apoptosis.

Adult ; Aged ; Biomarkers, Tumor ; metabolism ; Caspase 3 ; Caspases ; metabolism ; Down-Regulation ; Female ; Gastric Mucosa ; enzymology ; Humans ; Lymphatic Metastasis ; Lymphoma ; enzymology ; pathology ; Male ; Middle Aged ; Neoplasm Invasiveness ; PTEN Phosphohydrolase ; Phosphoric Monoester Hydrolases ; metabolism ; Stomach Neoplasms ; enzymology ; pathology ; Tumor Suppressor Proteins ; metabolism

The study was aimed to investigate the expression level of TRF1 protein in human acute leukemia and relationship between expression level of TRF1 protein and activity of telomerase. A quantitative Western blot technique was developed using anti-TRF1(33 - 277) monoclonal antibody and GST-TRF1 fusion protein as a standard to further determine the expression level of TRF1 protein in total proteins extracted from clinical specimens. 20 cases of acute leukemias were studied when 11 normal volunteer's bone marrow was used as control. The results showed that the expression level of TRF1 protein in normal bone marrow (2.217 +/- 0.461 microg/microl) was significantly higher than that in bone marrow of acute leukemia patients (0.754 +/- 0.343 microg/microl) (P < 0.01). There was no remarkable difference of expression level of TRF1 protein between ALL and ANLL (0.628 +/- 0.281 microg/microl vs 0.844 +/- 0.360 microg/microl, P > 0.05). After chemotherapy, TRF1 expression level of patients with complete remission raised (0.772 +/- 0.307 microg/microl vs 1.683 +/- 0.344 microg/microl, P < 0.01), but lower than that of normal (2.217 +/- 0.461 microg/microl, P < 0.01). TRF1 expression level of patients without complete remission was not remarkable different after chemotherapy (0.726 +/- 0.443 microg/microl vs 0.894 +/- 0.338 microg/microl, P > 0.05). TRF1 expression level of patients with complete remission was higher than that in patients without complete remession (1.683 +/- 0.344 microg/microl vs 0.894 +/- 0.338 microg/microl, P < 0.01). For all sample the telomerase activity was determined. It was confirmed that the activity of telomerase in normal bone marrow was lower than that in bone marrow of acute leukemia patients (0.125 +/- 0.078 microg/microl vs 0.765 +/- 0.284 microg/microl, P < 0.01). There was no significantly difference of expression level of TRF1 protein between ALL and ANLL (0.897 +/- 0.290 microg/microl vs 0.677 +/- 0.268 microg/microl, P > 0.05). After chemotherapy, telomerase activity of patients with complete remission reduced (0.393 +/- 0.125 microg/microl), but higher than that of normal (0.125 +/- 0.078 microg/microl, P < 0.01). It is concluded that expression level of TRF1 protein in AL patients is significantly decrese and associated with therapeutic efficaciousness and the activity of telomerase (P < 0.001).
Adolescent ; Adult ; Aged ; Bone Marrow Cells ; enzymology ; metabolism ; Child ; Female ; Humans ; Leukemia, Myeloid, Acute ; enzymology ; metabolism ; Male ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; enzymology ; metabolism ; Telomerase ; metabolism ; Telomeric Repeat Binding Protein 1 ; biosynthesis ; genetics

OBJECTIVETo determine whether the high level of asparagine synthetase (AS) expression in childhood acute lymphocytic leukemia (ALL) is associated with an inferior prognosis.

METHODSAS mRNA level in leukemic cells from 53 newly diagnosed ALL children was measured by real time fluorescent quantitative PCR method. Patients were divided into groups according to their relapse risk and outcome, and the AS expression levels in each group were compared. The survival rates in different AS expressing level groups were estimated and compared.

RESULTSThe highest level of AS [median 17.25 (2.48-46. 82)] was observed in children failed remission, intermediate level [14.28 (3.20-54.47)] in relapsed children and the lowest level [5.08 (0.84-54.92)] in children with continuous complete remission (CCR) (P<0.05). The AS mRNA level [14.93 (2.48-54.47)] in children with poor outcome (un-remission and relapsed) was significantly higher than that in children in CCR (P<0.01). The two-year estimated disease free survival was much lower in children with high AS expression (53.8%) than in those with low AS expression (84.6%) (P<0.05).

CONCLUSIONHigh expression of AS is associated with a poor outcome in ALL children.

Adolescent ; Aspartate-Ammonia Ligase ; metabolism ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; enzymology ; Prognosis

OBJECTIVETo study the expression of human telomere repeat binding factor 1 (TRF1) to investigate the correlation of telomerase activity with acute leukemia.

METHODSLeukemic cells were collected from 30 cases of acute leukemia. Realtime quantitative PCR with fluorescence probe hybridization was used to measure expression of TRF1 and hTERT mRNA in leukemic cells.

RESULTSTRF1 mRNA expression was 0.0126 (0.0127-0.0546) in acute non-lymphocytic leukemia (ANLL), which was lower than that in normal mononuclear cells [0.0457 (0.00839-0.262), P<0.001], but its expression in acute lymphoblastic leukemia (ALL) cells [0.0745 (1.92 x 10(-6)-0.193)] had no significant difference compared with that in normal mononuclear cells. TRF1 expression in ANLL cells was significantly lower than that in ALL cells (P=0.001). The expressions of TRF1 mRNA in AL cells and normal mononuclear cells had no significant correlation with expression of hTERT mRNA (r=-0.173, P=0.207).

CONCLUSIONThe expression of TRF1 is lower in ANLL cells, which indicates TRF1 may have some effect on telomerase activity by regulating telomere length in ANLL cells.

Adolescent ; Adult ; Aged ; Female ; Humans ; Leukemia, Myeloid, Acute ; enzymology ; metabolism ; Male ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; enzymology ; metabolism ; RNA, Messenger ; biosynthesis ; genetics ; Telomerase ; metabolism ; Telomeric Repeat Binding Protein 1 ; biosynthesis ; genetics

To explore the change of telomerase activity in acute leukemia (AL) cells and its relationship with cell cycle, PCR-ELISA was used to detect telomerase activity of bone marrow cells from 148 AL patients, including 92 cases with acute non-lymphocytic leukemia (ANLL) and 56 cases with acute lymphocytic leukemia (ALL). Thirty-six patients without bone marrow disorders were detected as normal control. The cell cycle of 16 patients and 4 controls was detected with flow cytometry. The results showed that the positive rate of telomerase was 71.6% (106/148) in the cells from AL patients, which was higher than that in the control group 5.6% (2/36). It was 88.9% (32/36) in the relapse group and 81.3% (61/75) in the untreated group. Both rates were higher than that in the CR group (35.1%, 13/37). There was no significant difference in the ALL and ANLL groups. The cell number in various phases of cell cycle had no significant difference between telomerase positive and negative groups. It was concluded that the activation of telomerase was very common in acute leukemia cells. Telomerase positive rate was closely associated with the different stages and progress of acute leukemia, and it might be a molecular marker for increased proliferation of leukemic cells during the process of the disease. Activation of telomeras had no correlation with cell number in different phases of cell cycle, while telomerase activity is modulated by other biological factors in addition to cell cycle.
Adult ; Cell Cycle ; physiology ; Child ; Enzyme-Linked Immunosorbent Assay ; methods ; Flow Cytometry ; Humans ; Leukemia, Myeloid, Acute ; enzymology ; pathology ; physiopathology ; Neoplasm Staging ; Polymerase Chain Reaction ; methods ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; enzymology ; pathology ; physiopathology ; Telomerase ; genetics ; metabolism