Increased C-MYC oncogene copy number detected with combined modified comparative genomic hybridization and FISH analysis in a Richter syndrome case with complex karyotype.

Modified comparative genomic hybridization (mCGH) was performed in a Richter syndrome case with a complex karyotype to identify and map gains of DNA sequences with possible importance in the pathogenesis and progression of the tumor. The mCGH analysis revealed a more intense signal on part of the long arm of one pair of chromosomes belonging to group C. The G-banding study showed that the increased DNA-sequence copy number originated from the 8q22-->qter chromosomal region.

Hypermethylation of p15/ink4b/MTS2 gene is differentially implicated among non-Hodgkin's lymphomas.

P15 (MTS2) gene is a candidate tumor suppressor gene localized adjacent to the p16 gene at 9p21. Deletions at the 9p21 region frequently affect both p16 and p15 genes, however, mutations in the coding sequence of the p15 gene have not been found in the majority of tumors analyzed, including non-Hodgkin's lymphomas. Abnormal methylation of the promoter region of p15 has been recently described as an alternative mechanism of inactivation of this gene.

[Correlation of flow and static cytometry; their application to the study of anaplastic lymphomas].

Purpose: DNA study by cytometric methods is one of the prognosis factors considered in malignant tumours. Flow cytometry (FCM) was the most frequently used techniques in cell suspensions. Image cytometry (ICM) was also applied in cellular smears and it is possible to measure the results with an Image Analyzer, which supposes a substancial advantage over DNA studies.

[Value of protein 53 expression in lymphoma. Its correlation with genetic mutations].

Purpose: p53 is a tumour suppressor gene encoding a nuclear phosphoprotein that plays an important role in the control of normal cell proliferation. We have tried to establish the value of expression of the p53 protein in malignant lymphomas and its correlation with the presence of structural gene abnormalities.

Material And Methods: 230 cases of lymphomas (11 Hodgkin's disease and 219 non-Hodgkin's) were studied by immunohistochemistry using an anti-p53 monoclonal antibody (DO-7, DAKO).

Correlation between mutations in p53 gene and protein expression in human lymphomas.

A discordance between p53 protein overexpression and the presence of mutations in the gene has been observed in many types of tumors, including human lymphomas. To probe this finding, we have studied a large series of 94 lymphomas of different pathologic types and histologic differentiation. Analyzing exons 5-9, we have found mutations in the p53 gene in 7 of 94 cases distributed in different subtypes: 4/12 (33%) high-grade B-cell non-Hodgkin's lymphomas (B-NHLs), in 1 of 5 (20%) high-grade mucosa-associated lymphomas (MALT), in 1 of 22 (4.

Role of nitric oxide in autocrine control of growth and apoptosis of endothelial cells.

Nitric oxide (NO) is a growth inhibitor for diverse cellular types. In the present study, we have found that the inhibition of NO production in bovine endothelial cells by an L-arginine competitive antagonist induces DNA replication and promotes the transition from prereplicative to replicative phases of the endothelial cell cycle and an increase in c-myc and c-fos oncogene-encoded protein expression. The inhibition of NO generation had, however, a markedly different outcome depending on the state of confluence of the cells, i.

[Clinico-morphologic reconsideration of anaplastic lymphoma. Retrospective study of 60 patients with aggressive clinical course and multiple recurrences].

Purpose: To identify anaplastic large cell lymphoma Ki-1+ (ALCL-Ki-1+) among a group of patients with aggressive Hodgkin's disease (HD) and to know the biological behaviour of the neoplasia (ALCL-Ki-1+).

Patients And Methods: Biopsies and clinical data of sixty patients with previous morphological diagnosis of HD lymphocytic depletion (LD), syncytial variant of nodular esclerosis (NE-II) and other subtypes of HD with aggressive clinical features were reviewed. A morphological, immunohistochemical (IHQ), proliferative and flow cytometric (FCM) studies were performed in lymph node biopsies.

Immunohistochemistry in apparently normal bone marrow trephine specimens from patients with nodal follicular lymphoma.

Aim: To establish the role of immunohistochemistry (using a limited panel of antibodies) in detecting minimal involvement by follicular lymphoma in routinely processed bone marrow trephine specimens, which show no obvious morphological (light microscopic) evidence of lymphoma; to determine whether bcl-2 immunostaining in bone marrow distinguishes between benign and malignant infiltrates in a patient with nodal follicular lymphoma.

Methods: Twenty seven consecutively selected paraffin wax embedded, formalin fixed bone marrow trephine specimens were stained with the following antibodies: anti-bcl-2, anti-CD79a, anti-CD3, and kappa and lambda light chains, using the Streptavidin biotin complex technique.

Results: Five of the 27 cases, which showed no evidence of involvement by follicular lymphoma on routine stains, showed monotypic B cells on immunohistochemistry.

[Large-cell anaplastic lymphomas: a genetic and immunophenotypic study].

Purpose: To characterize from a genetic point of view a group of non-Hodgkin's anaplastic large-cell lymphomas (ALCL) by Southern blot and PCR methods with different probes (molecular study) and with direct or post 24-78 hours cultures with GTC banding techniques (cytogenetic). To correlate the results to the immunophenotype performed with a complete panel of monoclonal antibodies (MoAb) according to avidin-biotine and alkaline phosphatase (APAAP) methods.

Material And Methods: Sixty cases of ALCL were reviewed and only 19 selected (with frozen or fresh material) because a complete immunohistologic and genotypic correlation had been done.

B-cell follicular lymphomas: clinical and biological characteristics.

Seventy cases of follicular B-cell lymphomas were studied: 37 cases derived from the follicular centre [27 centroblastic-centrocytic (CB-CC) and 10 centroblastic (CB)] and 33 from the mantle zone [mantle-cell lymphoma (ML)]. Presenting features as well as response to therapy, time free of symptoms and survival were reviewed. All the cases were diagnosed and classified with routine and immunohistochemistry methods.

DNA content in non-Hodgkin's lymphoma. Comparison between flow cytometry and cytogenetics in fresh and paraffin-embedded tissue.

DNA content of 36-non-Hodgkin's lymphomas was analyzed by flow cytometry (FCM) and cytogenetics (CG), 21 in fresh and 15 in paraffin-embedded tissue. The results of both techniques were coincident in 60% of the fresh tissue samples and in 45% of the paraffin-embedded ones, the reason for this difference could be the poor resolution of DNA histograms from paraffin-embedded tissue. All samples judged as aneuploid by FCM were aneuploid also by CG.

[Biology of secondary nodal follicular b-lymphomas. A patho-dynamic study].

Purpose: To assess the aggressivity factors and tumour prognosis in a series of non-Hodgkin lymphomas by the use of computer-quantified specific antibodies and flow cytometry.

Patients And Methods: Sixty-one cases of follicular B-cell lymphoma: 34 of the germinal centre (24 centroblastic-centrocytic, CB-CC, and 10 centroblastic, CC) and 27 of the follicular cortex (FCL), were studied. All the cases had been diagnosed between 1971 and 1992 at the Pathology Department of the Fundación Jiménez Díaz.

[Follicular mantle lymphoma: clinicopathologic and cell proliferation of 11 cases].

Background: The aim of the present was to study the biologic behavior of the lymphomas of the follicular mantle by analysis of different indexes of neoplastic cell proliferation and their relation with the clinical symptoms, prognosis and survival of the patients.

Methods: Light microscope, ultrastructural, and frozen and paraffin immunohistochemical studies were performed including the proliferative markers Ki-67 and PC10, flow cytometry and analysis of cell cycle in biopsy samples. Clinical data of 11 patients were collected in addition to therapeutic response and survival.

[Castleman's disease. A multifactorial study].

A case of Castleman's disease (hialino-vascular subtype) in a female patient 15-years-old is considered. Clinically there were isolated lymphadenopathies which relapsed after surgery and absence of general syndrome. Histoimmunological and electron microscopic studies were performed as DNA rearrangement and cytogenetics in order to exclude genetic abnormalities and monoclonality of this disorder.

A multiparametric study of malignant lymphoma of mucosa associated lymphoid tissue (MALT).

A morphological, immunophenotypic and ultrastructural study, cell cycle estimation, DNA and cytogenetic analysis were performed in ten cases of B-MALT lymphomas. Five had low grade lymphoma and five had high grade. Low and high grade cases showed the same cells but in different percentages: These included centrocyte-like cells with occasional monocytoid cytoplasmic changes, and centroblast-like cells.

Correlation between cytogenetic and molecular analysis of t(14;18) in follicular lymphomas.

A comparison between cytogenetic and molecular results of t(14;18) has been performed in 12 patients with follicular lymphomas: five nodular and seven diffuse. Ten cases showed cytogenetic alterations with different markers, including a 14q+ in eight: in four it was the result of a t(14;18). Molecular analysis by Southern blotting with bcl2 probes from major and minor cluster regions, and PCR with primers from major and minor regions showed differences versus the cytogenetic results.

[The immunological characterization of 63 cases of Hodgkin's disease with a panel of 8 antibodies].

Sixty three cases of Hodgkin's disease are studied (two with lymphonodular predominance, 15 with diffuse lymphocyte predominance, 26 nodular sclerosis, 15 mixed cell and 5 lymphocyte depletion) with a panel of 8 monoclonal antibodies, material routinely used and included in paraffin: Ber H2 (CD30), Leu M1 (CD15), Common Leukocyte Antigen (CD45), L26 (CD20), MB2, UCHL1 (CD45 RO), MTI (CD43) and Epithelial Membrane Antigen. Ber H2 turned out to be the most usefull marker, positive in 100% of cases, independently of the histologic type. Positiveness with Leu M1 ranged from 100% (2/2 cases) of lymphonodular predominance, to 53.

[Cytogenetic and molecular aspects in MALT lymphomas].

Cytogenetic and molecular results in 10 patients with extranodal lymphoma (MALT): 5 low grade and 5 high grade, were compared with the results observed in nodal lymphomas. This study suggests that there are cytogenetic differences between extranodal and nodal low grade lymphomas. Both molecular analysis by conventional Southern blot with probes for the major and minor regions of bcl-2 gene, and PCR analysis with primers from these regions, showed that t (14; 18) is a sporadic event in MALT lymphomas.

[Molecular analysis in 23 patients with T-lymphomas].

Gene rearrangement analysis has been performed in 23 patients with T-cell lymphoproliferative diseases: 4 cases with T-gamma lymphocytosis, one case of a Sezary's syndrome, one case of T-cell angioimmunoblastic lymphoma, two cases of T-cell lymphoepitheloid lymphoma, 11 patients with T-cell pleomorphic lymphoma, 3 cases of large anaplastic T-cell lymphoma and one case of T-cell lymphoblastic lymphoma. Rearranged banding patterns have been observed for at least one of the T-cell receptors (TCR) in 19 of the cases, and germ line configuration of the TCR and Ig genes in the other four. Likewise, both Ig and TCR rearrangements have been observed in three cases (one case of T-cell pleomorphic lymphoma, one case of large anaplastic T-cell lymphoma and one case of T-cell lymphoblastic lymphoma).

Immunophenotypic and Gene Rearrangement Analysis in Null- or T-Cell Neoplasias: Study of 16 Cases.

Immunophenotypic and molecular studies were performed in sixteen cases of T-cell lymphoproliferative disorders. These included eleven patients with peripheral T-cell lymphoma, two thymic lymphomas and three patients with T-gamma lymphocytosis. Peripheral T-cell lymphomas were of both low and high grades.

Ultrastructure of 26 cases of Ki-1 lymphomas: morphoimmunologic correlation.

Twenty-six cases of high-grade lymphomas with activation markers (CD30) classified and immunophenotyped according to the Kiel classification were studied to determine their fine structural features. Transmission electron microscopy showed in 17 cases anaplastic nuclear and cytoplasmic changes identical to those observed in Hodgkin's disease, it being impossible to determine by the morphology a B, T, or null nature. Four high-grade B-centroblastic and immunoblastic cases and five T-pleomorphic cases showed nuclear changes and cytoplasmic differentiation that suggested a T or B nature.