Expression of nitric oxide synthase isoforms and nitrotyrosine immunoreactivity by B-cell non-Hodgkin's lymphomas and multiple myeloma

Aims: 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. Methods and results: We studied the expression of NOS-IR isoforms and NY-IR in 16 cases of B-cell non-Hodgkin's lymphoma (NBL) (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 NBL, 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 NM, in a dot-like pattern in few tumour cells. Conclusions: 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.