Thymic epithelial tumors express vascular endothelial growth factors and their receptors as potential targets of antiangiogenic therapy: a tissue micro array-based multicenter study.

Objectives: Tumor angiogenesis is an essential and complex process necessary for the growth of all tumors which represents a potential therapeutic target. Angiogenesis inhibitors targeting vascular endothelial growth factor (VEGF) or their receptor tyrosine kinases have been approved by the FDA. In thymic epithelial tumors (TET), targeted therapies have been sporadically applied due to their rarity.

Utility of flow cytometry immunophenotyping in fine-needle aspirate cytologic diagnosis of non-Hodgkin lymphoma: A series of 252 cases and review of the literature.

Flow cytometry (FC) immunophenotyping of fine-needle aspiration (FNA) has been reported to be useful in the diagnosis of non-Hodgkin lymphomas (NHL). The authors reviewed their 5-year experience to assess the ability that FC has in improving the diagnostic capacity of cytomorphology in the diagnosis and subclassification of NHL according to the World Health Organization's classification. FC was performed on 252 FNA specimens.

The usefulness of flow cytometric CD10 detection in the differential diagnosis of peripheral T-cell lymphomas.

We studied the histologic and multiparameter flow cytometry (MFC) features of 12 cases of angioimmunoblastic T-cell lymphoma (AITL), 13 of mature T-cell lymphoma, and 25 control cases of reactive lymphoid hyperplasia to evaluate the role of CD10 in the differential diagnosis of peripheral T-cell lymphomas (PTCLs). A characteristic immunophenotypic profile (CD2+/CD4+) with recurrent phenotypic aberrancies (eg, CD3 and CD7 loss) was identified in most AITL cases; MFC documented CD10 coexpression on T cells in 10 (83%). Mature T-cell lymphoma showed a more heterogeneous altered immunophenotypic pattern, and 2 cases of PTCL, unspecified, had clear evidence of aberrant CD10 expression on T cells.

Transforming growth factor-beta binding receptor endoglin (CD105) expression in esophageal cancer and in adjacent nontumorous esophagus as prognostic predictor of recurrence.

Background: We hypothesized that the potent neovascularization marker endoglin (CD105), by differentially highlighting a subset of microvessels (MV) in esophageal cancer (EC), could provide better prognostic/therapeutic information than the panendothelial marker CD34, which also highlights MV.

Methods: Endoglin messenger ribonucleic acid (mRNA) expression in normal, malignant, and adjacent nontumorous esophagus tissue was quantified by real-time reverse-transcription polymerase chain reaction (RT-PCR). Sections of formalin-fixed, paraffin-embedded tissues were analyzed immunohistochemically for CD105 and CD34.

The tyrosine phosphatase Shp2 interacts with NPM-ALK and regulates anaplastic lymphoma cell growth and migration.

Anaplastic large cell lymphomas (ALCL) are mainly characterized by the reciprocal translocation t(2;5)(p23;q35) that involves the anaplastic lymphoma kinase (ALK) gene and generates the fusion protein NPM-ALK with intrinsic tyrosine kinase activity. NPM-ALK triggers several signaling cascades, leading to increased cell growth, resistance to apoptosis, and changes in morphology and migration of transformed cells. To search for new NPM-ALK interacting molecules, we developed a mass spectrometry-based proteomic approach in HEK293 cells expressing an inducible NPM-ALK and identified the tyrosine phosphatase Shp2 as a candidate substrate.

Functional validation of the anaplastic lymphoma kinase signature identifies CEBPB and BCL2A1 as critical target genes.

Anaplastic large cell lymphomas (ALCLs) represent a subset of lymphomas in which the anaplastic lymphoma kinase (ALK) gene is frequently fused to the nucleophosmin (NPM) gene. We previously demonstrated that the constitutive phosphorylation of ALK chimeric proteins is sufficient to induce cellular transformation in vitro and in vivo and that ALK activity is strictly required for the survival of ALK-positive ALCL cells. To elucidate the signaling pathways required for ALK-mediated transformation and tumor maintenance, we analyzed the transcriptomes of multiple ALK-positive ALCL cell lines, abrogating their ALK-mediated signaling by inducible ALK RNA interference (RNAi) or with potent and cell-permeable ALK inhibitors.

Cooperative induction of a tolerogenic dendritic cell phenotype by cytokines secreted by pancreatic carcinoma cells.

Ag presentation by dendritic cells (DC) is essential to effective antitumor T cell responses in cancer patients. Depending on their origin, maturation state, and the ambient cytokine milieu, DC can differentiate into distinct subpopulations, which preferentially either induce Th1 cell activation (CD11c+,CD123- myeloid DC (MDC)) or immunosuppressive T cell development (CD11c-,CD123+ plasmacytoid DC (PDC)). The present study was undertaken to characterize the effects of pancreatic carcinoma cell-derived cytokines on immature monocyte-derived DC (iMo-DC) in vitro and in vivo.

Prognostic significance of microvessel density and vascular endothelial growth factor expression in sinonasal carcinomas.

The prognostic significance of microvessel density and proliferative activity of the neoplastic cells, evaluated respectively by CD31 and Ki-67 positivity, and immunohistochemical expression of vascular endothelial growth factor (VEGF) was retrospectively investigated in 105 cases of sinonasal carcinoma (80 surgical specimens and 25 biopsies). The most represented histologic types were intestinal-type adenocarcinoma found in 36 patients (34.3%), squamous cell carcinoma (SCC) in 34 (32.

Intrasinusoidal bone marrow infiltration and splenic marginal zone lymphoma: a quantitative study.

Intrasinusoidal infiltration (ISI) is a pattern of invasion that is rarely found on bone marrow (BM) biopsies, and is considered as a hallmark of splenic marginal zone cell lymphoma (SMZL). We analysed BM biopsies showing intrasinusoidal infiltration from 54 consecutive patients with different types of lymphoma to verify if ISI quantity was a diagnostic criterion for SMZL. There were 35 primary splenic lymphoma (PSL) and 19 non-PSL; 28 SMZL, three non-splenic MZL, six mantle cell, six small lymphocytic, four follicular, four diffuse large B cell, one peripheral T cell, one lymphoplasmacytic and one anaplastic large-cell lymphoma.

Prevalence of Helicobacter pylori infection and intestinal metaplasia in subjects who had undergone surgery for gastric adenocarcinoma in Northwest Italy.

Aim: To investigate the seroprevalence of Helicobacter pylori (H pylori) infection and its more virulent strains as well as the correlation with the histologic features among patients who had undergone surgery for gastric cancer (GC).

Methods: Samples from 317 (184 males, 133 females, mean age 69+/-3.4 years) consecutive patients who had undergone surgery for gastric non-cardia adenocarcinoma were included in the study.

Incestuous paternity detected by STR-typing of chorionic villi isolated from archival formalin-fixed paraffin-embedded abortion material using laser microdissection.

Microscopic examination of a blood clot expelled by a physically and mentally disabled woman taken to the emergency room because of genital bleeding revealed the presence of chorionic villi encircled by decidua, hemorrhage, and necrosis. In order to identify the father of the product of conception, sections of formalin-fixed, paraffin-embedded abortion material were subjected to laser microdissection: DNA extraction from chorionic villi selectively isolated from the surrounding tissues allowed successful STR-typing of fetal cells, which was otherwise prevented by excess maternal DNA. The large number of homozygous genotypes in the fetal profile suggested incestuous paternity.

Ablation of oncogenic ALK is a viable therapeutic approach for anaplastic large-cell lymphomas.

Anaplastic large-cell lymphomas (ALCLs) carry chromosome translocations in which the anaplastic lymphoma kinase (ALK) gene is fused to several partners, most frequently, the NPM1 gene. We have demonstrated that the constitutive activation of ALK fusion proteins results in cellular transformation and lymphoid neoplasia. Herein, we specifically down-regulated ALK protein expression by using small hairpin RNA (shRNA) targeting a sequence coding for the catalytic domain of ALK.

p130Cas mediates the transforming properties of the anaplastic lymphoma kinase.

Translocations of the anaplastic lymphoma kinase (ALK) gene have been described in anaplastic large-cell lymphomas (ALCLs) and in stromal tumors. The most frequent translocation, t(2;5), generates the fusion protein nucleophosmin (NPM)-ALK with intrinsic tyrosine kinase activity. Along with transformation, NPM-ALK induces morphologic changes in fibroblasts and lymphoid cells, suggesting a direct role of ALK in cell shaping.

Follicular origin of a subset of CD5+ diffuse large B-cell lymphomas.

Most follicular lymphomas (FLs) have a phenotype consistent with the origin from CD5-, CD10+, bcl-6+ follicular center cells and can progress to diffuse large B-cell lymphoma (DLBCL). CD5 is expressed in about 10% of DLBCLs, showing prognostic value, whereas expression is rare in FL. We present 6 cases with coexisting features of CD5+ FL and CD5+ DLBCL, supporting a follicular origin for some CD5+ DLBCLs.

Relationship between AgNORs, MIB-1 and oncogene expression in male breast carcinoma and papillary superficial bladder neoplasm.

The expression of p53, c-erbB-2, bcl-2 and c-myc proteins was compared to the quantity of the nucleolar organiser regions (AgNORs) and MIB-1 antigen to elucidate the relationship between oncogene expression and rapidity of cell proliferation and tumor growth fraction. Sections from 50 male breast carcinomas (MBC) and 62 superficial papillary bladder neoplasias were stained with the standardised AgNOR method and monoclonal antibodies MIB-1, DO7, CB11, bcl-2 124 and 9E11. p53 immunopositivity was associated with high AgNOR quantity and MIB-1 scores both in MBC and bladder neoplasm.

Immunohistochemical expression analysis of the human interferon-inducible gene IFI16, a member of the HIN200 family, not restricted to hematopoietic cells.

This is the first description of an extensive immunohistochemical analysis of interferon (IFN)-inducible gene IFI16 expression in normal tissues. Immunohistochemical detection of IFI16 in paraffin-embedded tissues is achieved by using a polyclonal antibody raised against its C-terminal fragment that recognizes its three closely migrating isoforms in Western blotting. The results clearly indicate that IFI16 expression is not restricted to the hematopoietic compartment.

S-phase kinase-associated protein 2 expression in non-Hodgkin's lymphoma inversely correlates with p27 expression and defines cells in S phase.

The protein expression of the cyclin-dependent kinase inhibitor p27 is often deregulated in human tumors. In lymphomas the inactivation of p27 is achieved through either increased degradation(1) or sequestration via D cyclins,(2) and p27 protein levels have been shown to have a prognostic significance.(1,3) Recently, S-phase kinase-associated protein 2 (Skp2) has been proved to mediate p27 degradation in normal cells(4-7) and to have oncogenetic properties.