Epstein-Barr Virus-Induced Gene 3 (EBI3): A Novel Diagnosis Marker in Burkitt Lymphoma and Diffuse Large B-Cell Lymphoma

The distinction between Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL), two types of mature aggressive B-cell lymphomas that require distinct treatments, can be difficult because of forms showing features intermediate between DLBCL and BL (here called BL/DLBCL). They can be discriminated by the presence of c-myc translocations characteristic of BL. However, these are not exclusive of BL and when present in DLBCL are associated with lower survival. In this study, we show that Epstein-Barr virus-induced gene 3 (EBI3) is differentially expressed among BL and DLBCL. Analysis of gene expression data from 502 cases of aggressive mature B-cell lymphomas available on Gene Expression Omnibus and immunohistochemical analysis of 184 cases of BL, BL/DLBCL or DLBCL, showed that EBI3 was not expressed in EBV-positive or -negative BL cases, whereas it was expressed by over 30% of tumoral cells in nearly 80% of DLBCL cases, independently of their subtypes. In addition, we show that c-myc overexpression represses EBI3 expression, and that DLBCL or BL/DLBCL cases with c-myc translocations have lower expression of EBI3. Thus, EBI3 immunohistochemistry could be useful to discriminate BL from DLBCL, and to identify cases of BL/DLBCL or DLBCL with potential c-myc translocations

Etude rétrospective de 33 tumeurs du cordon spermatique (apport des nouveaux critères diagnostiques morphologiques, immunohistochimiques et cytogénétiques dans la classification des tumeurs mésenchymateuses. Place des liposarcomes)

Les sarcomes sont les tumeurs solides qui ont le plus bénéficié des avancées de la cytogénétique et de la biologie moléculaire. Les liposarcomes bien différenciés et dédifférenciés sont des sarcomes à cytogénétique simple caractérisés par l amplification du gène MDM2. Cette amplification est suspectée en immunohistochimie par la surexpression de la protéine MDM2 et peut être confirmée par hybridation in situ révélée par fluorescence (FISH) ou par chromogène (CISH). Nous avons revu et reclassé 33 tumeurs mésenchymateuses du cordon spermatique selon les nouveaux critères de diagnostic morphologiques, immunohistochimiques et cytogénétiques. Pour cette étude nous avons mis au point la CISH MDM2 sur tissu fixé et inclus en paraffine. La série comporte après relecture 2/3 de liposarcomes bien différenciés et dédifférenciés. La moitié des liposarcomes dédifférenciés n avait pas été diagnostiquée. En se dédifférenciant, les liposarcomes peuvent prendre des aspects de différenciation divergente notamment musculaire et sont souvent à tort diagnostiqués comme des sarcomes appartenant à une autre ligne de différenciation. Pour établir le diagnostic, le pathologiste doit rechercher minutieusement un contingent de liposarcome bien différencié associé, rechercher la surexpression de MDM2 en immunohistochimie et mettre en évidence l amplification de MDM2, possible par CISH. Ce diagnostic ne doit pas être méconnu en raison de la nécessité d une prise en charge thérapeutique adaptée, différentes de celle des autres sarcomes.PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocSudocFranceF

Expression of IL-27 by tumor cells in invasive cutaneous and metastatic melanomas [corrected]..

Interleukin (IL)-27 is a cytokine of the IL-12 family that displays either immunostimulatory or immunosuppressive functions depending on the context. In various murine tumor models including melanoma models, ectopic expression of IL-27 has been shown to play an anti-tumoral role and to favor tumor regression. In this study, we investigated whether IL-27 might play a role in the development of melanoma in humans. We analyzed the in situ expression of IL-27 in melanocytic lesions (n = 82) representative of different stages of tumor progression. IL-27 expression was not observed in nevus (n = 8) nor in in situ melanoma (n = 9), but was detected in 28/46 (61%) cases of invasive cutaneous melanoma, notably in advanced stages (19/23 cases of stages 3 and 4). In most cases, the main source of IL-27 was tumor cells. Of note, when IL-27 was detected in primary cutaneous melanomas, its expression was maintained in metastatic lesions. These in situ data suggested that the immunosuppressive functions of IL-27 may dominate in human melanoma. Consistent with this hypothesis, we found that IL-27 could induce suppressive molecules such as PD-L1, and to a lesser extent IL-10, in melanoma cells, and that the in situ expression of IL-27 in melanoma correlated with those of PD-L1 and IL-10

Expression of follicle-stimulating hormone receptor by the vascular endothelium in tumor metastases.

International audienceBACKGROUND: The Follicle Stimulating Hormone receptor (FSHR) is expressed by the vascular endothelium in a wide range of human tumors. It was not determined however if FSHR is present in metastases which are responsible for the terminal illness. METHODS: We used immunohistochemistry based on a highly FSHR-specific monoclonal antibody to detect FSHR in cancer metastases from 6 major tumor types (lung, breast, prostate, colon, kidney, and leiomyosarcoma ) to 6 frequent locations (bone, liver, lymph node, brain, lung, and pleura) of 209 patients. RESULTS: In 166 patients examined (79%), FSHR was expressed by blood vessels associated with metastatic tissue. FSHR-positive vessels were present in the interior of the tumors and some few millimeters outside, in the normally appearing tissue. In the interior of the metastases, the density of the FSHR-positive vessels was constant up to 7 mm, the maximum depth available in the analyzed sections. No significant differences were noticed between the density of FSHR-positive vessels inside vs. outside tumors for metastases from lung, breast, colon, and kidney cancers. In contrast, for prostate cancer metastases, the density of FSHR-positive vessels was about 3-fold higher at the exterior of the tumor compared to the interior. Among brain metastases, the density of FSHR-positive vessels was highest in lung and kidney cancer, and lowest in prostate and colon cancer. In metastases of breast cancer to the lung pleura, the percentage of blood vessels expressing FSHR was positively correlated with the progesterone receptor level, but not with either HER-2 or estrogen receptors. In normal tissues corresponding to the host organs for the analyzed metastases, obtained from patients not known to have cancer, FSHR staining was absent, with the exception of approx. 1% of the vessels in non tumoral temporal lobe epilepsy samples. CONCLUSION: FSHR is expressed by the endothelium of blood vessels in the majority of metastatic tumors

Quelle est la place des inhibiteurs calciques lorsque les bêta-bloquants sont contre-indiqués dans le traitement du post-infarctus du myocarde ?

Cet article se propose d'examiner les bénéfices du traitement par inhibiteur calcique dans le post-infarctus du myocarde à travers les principales études randomisées évaluant cette thérapeutique. Il apparaît évident que ces essais cliniques ont été quasiment tous menés avant l'ère de la reperfusion et semblent par conséquent obsolètes. En outre, aucun essai thérapeutique n'a permis de démontrer un bénéfice du traitement par inhibiteur calcique sur la mortalité dans le post-infarctus du myocarde. En conclusion, nul ne sait si cette classe thérapeutique n'a un quelconque intérêt en comparaison avec un placebo dans la prévention secondaire du post-infarctus du myocarde, sachant que des effets secondaires potentiellement dangereux, liés à leur prescription, peuvent survenir

Efficient ex vivo gene transfer into non-human primate hepatocytes using HIV-1 derived lentiviral vectors.

International audienceBACKGROUND/AIMS: Lentivirus-mediated ex vivo gene therapy is becoming a promising approach for the treatment of liver metabolic disorders. However, the feasibility of this approach needs to be studied in large animal models. The purpose of this study was to evaluate the efficacy of ex vivo gene transfer into Macaca hepatocytes with two different HIV-1 derived lentiviral vectors. METHODS: A self-inactivating lentivector was constructed to express GFP under the control of the hepatic apolipoprotein A-II promoter. Freshly isolated and thawed hepatocytes were transduced in suspension with lentiviral vectors expressing the GFP gene under the control of a ubiquitous promoter (EF1-alpha) and the apolipoprotein A-II promoter. Transduced thawed hepatocytes were transplanted into the spleen of newborn mice, and livers analyzed 4 and 12 weeks after transplantation. RESULTS: We show that lentivectors are efficient in transducing hepatocytes in suspension either freshly isolated or cryopreserved. We also show that thawed and transduced hepatocytes engrafted and participated in liver growth after transplantation into newborn mice and that the apolipoprotein A-II promoter is functional. CONCLUSIONS: Our data show that transplantation of transduced hepatocytes into monkeys should allow to evaluate the fate of transplanted cells and transgene expression in a pre-clinical model of ex vivo gene therapy

Characteristics of mature aggressive B-cell lymphomas analyzed by immunohistochemistry.

<p>Characteristics of mature aggressive B-cell lymphomas analyzed by immunohistochemistry.</p

Analysis of IL-10 induction by IL-27 in melanoma.

<p>(A) Constitutive expression of IL-27Rα and gp130 was analyzed by FACS on 4 melanoma cell lines as indicated. (B) Expression of <i>IL-10</i> was analyzed by qPCR in the A375 melanoma cell line cultured for 3 days in the presence or absence of IL-27 or TGF-ß1. (C) Supernatants from the A375 cell line cultured for 3 and 4 days in the presence or absence of IL-27 or TGF-ß1 were tested for IL-10 by ELISA. A representative experiment of 3 is shown in (B) and (C). (D) Distribution of cases that expressed IL-10 or not, among IL-27-negative or -positive cutaneous and metastatic melanomas. (E) Staining for IL-10 in a case of a primary cutaneous melanoma and a case of metastatic melanoma that were positive for IL-27. The bar represents 100 µM.</p