3-nitrotyrosine and Lymphoma--B-Cell

Although oxidative stress plays an important role in the biology of solid malignant tumors, little is known about oxidative stress in hematological malignancies. In this study, we evaluated the immunohistochemical expression and clinical correlations of oxidative stress markers and several essential antioxidant enzymes in B-cell lymphomas. Paraffin-embedded diagnostic tissue samples from 18 diffuse large B-cell lymphomas (DLBCL), 18 follicular lymphomas (FL), 19 Hodgkin lymphomas (HL), 7 chronic lymphocytic leukemias (CLL), 7 mantle cell lymphomas (MCL) and 7 mucosa-associated lymphoid tissue (MALT) lymphomas, together with samples from 6 reactive lymph nodes were stained for oxidative stress markers 8-hydroxydeoxyguanosine (8-OHdG) and nitrotyrosine and antioxidant enzymes manganese superoxide dismutase (MnSOD), thioredoxin (Trx) and γ-glutamyl cysteine synthetase (γ-GCS). There was increased 8-OHdG reactivity in DLBCL compared to more indolent lymphomas and reactive lymph nodes. Positivity for Trx was most intense in HL. In DLBCL, positivity for 8-OHdG and nitrotyrosine associated with shorter survival (p = 0.032 and p = 0.026, respectively). This study showed increasing expression of oxidative stress markers and antioxidant enzymes in a series of lymph node samples evolving from reactive lymph nodes to indolent and aggressive lymphomas. These markers seem to have strong prognostic value, but this has to be verified in larger studies.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adult; Biomarkers, Tumor; Deoxyguanosine; Disease-Free Survival; Female; Glutamate-Cysteine Ligase; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Lymph Nodes; Lymphoma, B-Cell; Male; Middle Aged; Oxidative Stress; Prognosis; Reproducibility of Results; Sensitivity and Specificity; Superoxide Dismutase; Thioredoxins; Tyrosine

Nitric oxide synthases (NOS) are isoenzymes that catalyse the synthesis of nitric oxide (NO). The three main NOS isoforms are: NOS1 or neuronal, NOS2 or inducible, and NOS3 or endothelial. NO plays both physiological and pathological roles, depending on its rate of synthesis and concentration, cellular source and microenvironment. Apoptosis is an important biological factor in low-grade lymphomas, and NO is able to prevent apoptosis. In-situ expression of NOS and synthesis of NO have been shown in several malignant tumours, but not in lymphoid neoplasms. This study evaluates whether human B-cell neoplasms express NOS isoforms, and nitrotyrosine (NY), which is usually interpreted as a marker of NO.. We studied the expression of NOS-IR isoforms and NY-IR in 16 cases of B-cell non-Hodgkin's lymphoma (NHL) (five follicle centre cell lymphoma, four small lymphocytic/CLL, and seven diffuse large cell lymphoma), and 10 cases of multiple myeloma (MM). NOS1 was expressed in 5/10 cases of MM, and 15/16 cases of NHL. NOS2 was detected in all cases of MM, and in 14/16 cases of NHL, whereas NOS3 was positive in 3/10 of MM and in only in 1/16 cases of NHL. The expression of NY-IR was observed in 70% of MM cases, and in all cases of B-cell NHL, in a dot-like pattern in few tumour cells.. B-cell neoplasms express neuronal and inducible NOS, and nitrotyrosine. Taken together, our results suggest that B-cell neoplasms can produce NO. The role of NO in the biology, diagnosis and prognosis of B-cell neoplasms remains to be established.

Topics: Adult; Aged; Cell Nucleus; Cytoplasm; Female; Humans; Immunohistochemistry; Isoenzymes; Lymphoma, B-Cell; Male; Middle Aged; Multiple Myeloma; Nitric Oxide Synthase; Tyrosine