S U M M A R Y Sphingosine-1-phosphate (S1P), a potent lipid mediator, transduces intracellular signals through the activation of S1P receptors (S1PRs). Although S1PRs have been shown to play an important role in the central nervous system (CNS), accurate localization and the function of S1PR1 in the human CNS are still unclear. In this study, we investigated the localization of S1PR1 in the human CNS of postmortem samples, using a rabbit polyclonal antibody, the specificity of which had been well defined. Immunohistochemical investigation of paraffin-embedded sections revealed diffuse granular staining of the gray matter. The signals of the gray matter were much stronger than those of the white matter. The immunohistochemical expression levels correlated well with the results of quantitative real-time RT-PCR-based analysis and Western blotting. Studies using double immunostaining and immunoelectron microscopy revealed that the antigen was strongly expressed in the membrane of the astrocytic foot processes of glia limitans and astrocytes with radial cytoplasm, but not distributed in neurons. In neurological disorders, hypertrophic astrocytes with strong expression of glial fibrillary acidic protein exhibited significantly decreased expression of S1PR1 in contrast to its strong expression in astrocytes forming fibrillary gliosis. These results indicate that S1PR1 is localized in astrocytes, and its expression level may change during the processes that occur after brain damage. (J Histochem Cytochem 58:847-856, 2010)

The distribution and pathological significance of sphingosine-1-phosphate receptor 1 expression are still unclear. In this study, we evaluated sphingosine-1-phosphate receptor 1's suitability as a diagnostic marker for malignant lymphoma by immunostaining formalin-fixed paraffin-embedded sections using a well-defined commercial anti-sphingosine-1-phosphate receptor 1 antibody. Sphingosine-1-phosphate receptor 1 was strongly expressed on the surface of small lymphocytes forming primary lymphoid follicles and in the mantle zone of secondary lymphoid follicles. Microarray-based immunohistochemistry with tissue samples from 85 lymphoid malignancy cases demonstrated that sphingosine-1-phosphate receptor 1 was expressed on the surface of mantle cell lymphoma cells. Strong expression was observed in all classical mantle cell lymphoma cases involving the lymph node (19 out of 19), gastrointestinal tract (10 out of 10), bone marrow (9 out of 9), and orbita (1 out of 1). Good results were obtained even in sections where cyclin D1 signals were lost because of over-fixation and/or decalcification. One aggressive variant of mantle cell lymphoma displayed a weaker membranous staining than classical mantle cell lymphoma in the lymph node and bone marrow. In a cyclin D1-negative mantle cell lymphoma of the orbita, no conclusive result was obtained. No cases of follicular lymphoma, marginal zone lymphoma, B lymphoblastic leukemia/lymphoma, or Burkitt's lymphoma showed any significant expression, whereas 2 out of 6 chronic lymphocytic leukemia/small lymphocytic lymphomas in bone marrow, 1 out of 3 lymphoplasmacytic lymphomas in the lymph node, and 2 out of 37 diffuse large B-cell lymphomas exhibited staining. A quantitative reverse transcription polymerase chain reaction-based analysis of mantle cell lymphoma lines revealed the sphingosine-1-phosphate receptor 1 mRNA expression level to be well correlated with the results of immunocytochemistry, flow cytometry, and western blotting. Thus, sphingosine-1-phosphate receptor 1 immunohistochemistry may be useful in the histological diagnosis of mantle cell lymphoma with formalin-fixed and paraffin-embedded sections. The antigen may be particularly valuable in cases where cyclin D1 immunostaining is not successful.

Sphingosine-1-phosphate (S1P) is a potent lipid mediator that is produced during the metabolism of sphingolipid by sphingosine kinase. S1P has been implicated in the migration and trafficking of lymphocytes and several lymphoid malignancies through S1P receptors. Moreover, the overexpression of sphingosine-1-phosphate receptor 1 (S1PR1) has been correlated with the constitutive activation of signal transducer and activator of transcription (STAT)3 and poor prognosis of diffuse large B-cell lymphoma (DLBCL). Thus, in this study, we examined the expression of S1PR1 in 198 DLBCL samples collected from nodal and various extranodal sites and sub-classified formalin-fixed paraffin-embedded tissue samples into germinal centre B-cell-like (GCB) and non-GCB subgroups using immunohistochemistry. These analyses showed S1PR1 overexpression in 15·7% of all cases with DLBCL and in 54·2% of 24 cases with primary testicular (PT)-DLBCL; S1PR1 expression correlated with S1PR1mRNA expression and STAT3 phosphorylation in fresh samples. Analyses of data from a single institution suggested that S1PR1 overexpression was an independent negative prognostic marker in 68 patients with DLBCL of clinical stages I and II. The present high prevalence of S1PR1 overexpression warrants the consideration of PT-DLBCL as a distinct disease subtype and suggests the potential of the S1P/S1PR1 axis as a therapeutic target.

No abstract

No abstract

Cardioembolic stroke due to tumor emboli is a rare complication of neoplasm. A patient with metastatic cardiac liposarcoma who suffered from embolic stroke is reported. Autopsy confirmed that the cardiac tumor was a metastatic liposarcoma from the retroperitoneum, and the cerebral vessel was occluded by tumor cells and fibrin clot.

No abstract

No abstract