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Biomedical subjects

A Gloghini

Publications and source records attributed to A Gloghini.

At least 127 records · Page 7Linked to original sources
PubMed1995

Genotypic and immunohistological demonstration of the progression of an unusual reactive-like B-cell lymphoproliferative disorder to a high grade diffuse lymphoma.

In the present study the clinical and pathological evolution of a reactive-like B-cell lymphoproliferative disorder with an unusually high content of T cells is described. Immunogenotypic analysis showed that the same phenotypically atypical B-cell clone, characterized by the unusual presence of an immunoglobulin (Ig)K gene rearrangement, with the heavy chain (IgH) gene in germline configuration, was invariantly present in all phases of the disease. The disorder showed an indolent course for a long period of time during which the clonal B-cell population coexisted with an abundant, reactive T-cell component in different locations of the disease. These findings, together with the observation of spontaneous progression and regression phases of the disorder and its responsiveness to corticosteroids, suggest that functional interactions between the B-cell clone and the polyclonal infiltrating T cells probably were involved in the pathogenesis of the disease. After the administration of the antiblastic treatment, a progressive reduction of the reactive T-cell component was observed with the concomitant evolution to a diffuse large cell (immunoblastic) B-cell lymphoma and the appearance of an IgH gene rearrangement. The biological characteristics and the clinical evolution of the case described here are similar to those reported for the so-called "T-cell-rich B-cell lymphomas" (TCRBCLs). These findings suggest that the T-cell-rich pattern may identify a group of B-cell lymphoproliferations with common pathogenetic mechanisms and clinical behavior.

Adult↗
PubMed1995

Expression of the monomeric 67-kd laminin-binding protein in human lymphomas as defined by MLuC5 monoclonal antibody and paraffin section immunohistochemistry.

Interactions between cancer cells and laminin, a major component of basement membranes, are mediated through a large variety of cell surface proteins designated as laminin receptors. Among the above proteins, a 67-kd monomeric high affinity laminin receptor (67 LR) has long been suspected to be involved in tumor progression. In this study we wished to establish whether the 67 LR molecule is detectable on tumor cells of Hodgkin's disease (HD) and non-Hodgkin's lymphomas (NHLs), to define its pattern of expression, and to assess the potential utility of 67 LR in differentiating these pathological entities. Morphological and immunohistological studies were performed on 85 specimens of HD and a series of 334 NHL specimens, including anaplastic large cell (ALC) (CD30-positive) lymphomas (73 specimens). For immunohistochemical assessment of the 67 LR we used the monoclonal antibody (MoAb) MLuC5 directed against the 67-kd laminin receptor on paraffin-embedded sections. Reed-Sternberg cells reacted with MLuC5 MoAb in four of 85 (4.7%) HD specimens. Among the NHL specimens, a MLuC5-positive reaction was expressed in 3.3% of B-cell lymphomas. They all belonged to the high grade subtypes. On the other hand, a MLuC5-positive reaction was detected in none of the T-cell lymphomas tested. In contrast to the results obtained with the other NHLs, in 30.2% of ALC (CD30-positive) lymphoma specimens, tumor cells reacted with MLuC5 MoAb. MLuC5-expressing ALC (CD30-positive) lymphoma cells were of either T-cell (six of 17 specimens), B-cell (three of 25 specimens), or undetermined phenotype (10 of 31 specimens). Our investigation has shown that 67 LR as shown by MLuC5 MoAb is detectable only in neoplastic cells of a fraction of ALC (CD30-positive) lymphomas and small subsets of B-cell high grade NHLs and HD. The restricted expression of the 67 LR molecule to ALC (CD30-positive) lymphomas provides a potential tool for the phenotypic separation of this pathological entity from HD and other lymphomas. Whether the detection of the 67 LR expression in these lymphoma subsets may be related to the aggressiveness of the disease remains to be ascertained.

Antibodies, Monoclonal↗
PubMed1995

KP1/CD68 expression in malignant neoplasms including lymphomas, sarcomas, and carcinomas.

Expression of KP1/CD68 macrophage-associated antigen in a series of 840 selected malignant neoplasms, including immunomorphologically characterized cases of non-Hodgkin's lymphoma (NHL) (434), Hodgkin's disease (HD) (115), soft tissue sarcoma (147), carcinoma (49), and other tumors (95), was examined. KP1 expression was detected in a significant number of NHLs (107 of 434; 24.7%), most of them (65 of 107; 60.7%) of the diffuse small cell subtype. Only 14 of the 155 large cell lymphomas, compared to 10 of the 51 Ki-1/CD30+ anaplastic large cell (ALC) lymphomas examined, were KP1 positive. Conversely, none of the T-lineage NHL--other than Ki-1/CD30+ ALC lymphomas--or the HD cases tested was labeled by KP1 antibody. Among the other neoplasms tested, KP1 was reactive with a variable proportion of cases of malignant fibrous histiocytoma (19 of 24; 79.2%), malignant schwannoma (8 of 22; 36.4%), liposarcoma (3 of 9; 33.3%), leiomyosarcoma (8 of 37; 21.6%), cutaneous or metastatic melanoma (51 of 73; 69.9%), and renal cell carcinoma (3 of 5; 60%). These results indicate that KP1 shows a relatively wide spectrum of immunoreactivity with malignant neoplasms of presumed non-histiocyte origin, thus arguing against its expected specificity and high value in diagnostic pathology. Although the significance of KP1 expression by some subsets of NHLs remains to be elucidated, its close association with B-cell NHLs, mostly of the diffuse small cell type, should stimulate further pathologic and clinical investigations.

Antibodies, Monoclonal↗
PubMed1995

AIDS-related Burkitt's lymphoma. Morphologic and immunophenotypic study of biopsy specimens.

In patients infected with HIV, high-grade B-cell non-Hodgkin's lymphomas (NHL), including the small noncleaved cell (SNCC) category, exhibit pleomorphic features, which makes precise definition difficult. Sixty-nine pathologic specimens with HIV-related systemic lymphomas, including 42 SNCC, 20 immunoblastic lymphomas (IBL), and 7 cases with features "intermediate" between SNCC and IBL were morphologically and immunophenotypically investigated. The host immune status was also analyzed in 57 of 69 patients. In 29 representative SNCC lymphomas, in 9 IBL cases, and an additional 3 intermediate lymphomas, both p53 protein overexpression and the association of Epstein-Barr virus (EBV) genetic information were assessed. Small noncleaved cell lymphomas included tumors exhibiting features of the 2 established subtypes (27 Burkitt's and 15 non-Burkitt's). In the seven intermediate cases, cells showed features intermediate between SNCC with plasmablastic differentiation and immunoblasts plasmacytoid. Immunoblast-like cells were also present. p53 protein overexpression and EBV association were found in a proportion of SNCC (14 of 29; 7 of 29) and intermediate (3 of 3; 2 of 3) lymphomas. Conversely, IBL cases were consistently p53 negative, but showed a high EBV association (7 of 9). All the evaluated patients with intermediate lymphomas had a considerably lower mean (76.6 per mm3 +/- 77.4 SD) and median (54 per mm3) number of CD4+ lymphocyte count than SNCC patients (mean 227.9 per mm3 +/- 186.9 SD, median 193 per mm3), thus mirroring IBL patients (mean 95.3 per mm3 +/- 82.8 SD, median 81 per mm3). All data provide evidence that lymphomas showing intermediate features constitute a distinct subgroup from either SNCC or IBL.

Biopsy↗
PubMed1995

High frequency of CD45RO expression in AIDS-related B-cell non-Hodgkin's lymphomas.

Although immunophenotypic abnormalities have been reported in B-cell non-Hodgkin's lymphomas (NHLs) occurring in the general population, there are no extensive studies on such abnormalities in AIDS-related B-cell NHLs. Reactivity of CD45RO/UCHL1 and expression of other T-cell associated antigens (CD43, OPD4, CD3, CD5, EMA) were examined by immunohistochemistry in 66 diffuse aggressive AIDS-related B-cell NHLs and in 296 AIDS-unrelated B-cell NHLs of similar morphology analyzed in the same institution. EBER in situ hybridization studies were also carried out in 57 of the 66 AIDS-related B-cell NHLs investigated. CD45RO/UCHL1 was expressed in 27% of AIDS-related B-cell NHLs, but only in 8% of diffuse aggressive AIDS-unrelated B-cell NHLs. The difference was highly significant (P < .001) overall and, within the Working Formulation subtypes, especially marked among small noncleaved cell (SNCC) lymphomas. Conversely, the reactivity of other T-cell associated antigens seemed to be very similar in AIDS-related and AIDS-unrelated NHLs. However, for CD43, a significantly lower number of positive cases was found in AIDS-related NHLs among SNCC lymphomas. Among AIDS-related B-cell NHLs, the highest frequency of CD45RO/UCHL1 expression was found in the immunoblastic subset with plasmacytoid differentiation. In the latter CD45RO/UCHL1 preferentially associated with EMA expression and EBV infection of the tumor clone, but not with CD45RA. The present finding of an excess of CD45RO/UCHL1 expression in AIDS-related B-cell lymphomas may reflect the preferential expansion of CD45RO expressing B-cell clones with putative autoreactive potential, as suggested by the expansion of CD45RO expressing B-cells in autoimmune disorders.

Antibodies, Monoclonal↗
PubMed1995

Distribution of Kaposi's sarcoma herpesvirus sequences among lymphoid malignancies in Italy and Spain.

In this study we have tested the distribution of Kaposi's sarcoma herpesvirus (KSHV) DNA sequences throughout the spectrum of lymphoid neoplasia in Italy and Spain. 180 cases of lymphoid malignancies representative of the major histologic and immunophenotypic categories of B- and T-cell tumours were analysed by means of a polymerase chain reaction-based assay. KSHV sequences were consistently absent in all categories of lymphoid malignancies studied, with the exception of a subset of B-cell non-Hodgkin's lymphomas localizing in the pleural, pericardial or peritoneal cavities, and fulfilling the diagnostic criteria of body-cavity-based lymphoma. The selective and consistent association of KSHV sequences with cases of body-cavity-based lymphoma throughout the spectrum of lymphoid neoplasms suggests that KSHV may be involved in the pathogenesis of this peculiar type of lymphoid malignancy.

Base Sequence↗
PubMed1995

CD30 (Ki-1)-positive anaplastic large-cell lymphomas in 13 patients with and 27 patients without human immunodeficiency virus infection: the first comparative clinicopathologic study from a single institution that also includes 80 patients with other human immunodeficiency virus-related systemic lymphomas.

PURPOSE: CD30 (Ki-1)-positive anaplastic large-cell lymphoma (Ki-1 ALCL) rarely has been described in patients with human immunodeficiency virus (HIV) infection. The purpose of this study was to characterize further the clinicopathologic features of Ki-1 ALCL in patients with HIV infection and, for the first time, to make a comparison with Ki-1 ALCL in patients without HIV infection. PATIENTS AND METHODS: From September 1987 to April 1993, 93 patients with HIV infection and systemic non-Hodgkin's lymphoma (NHL) were treated at the Cancer Center of Aviano, Italy; in 13 (14%), the diagnosis was of Ki-1 ALCL subtype. This group of patients was compared with the remaining 80 patients who had other HIV-related NHL and with another group of 27 patients with Ki-1 ALCL who were without a diagnosis of HIV infection. RESULTS: There was no case of a T-cell phenotype in the 13 HIV-positive Ki-1 ALCL patients, whereas there was such a phenotype in six of 27 (22%) HIV-negative Ki-1 ALCL patients. In regard to the general characteristics of the two groups with Ki-1 ALCL, more patients with stage IV, two or more extranodal sites at presentation, treatment-related leukopenia, and opportunistic infections as the cause of death were observed in the HIV-positive Ki-1 ALCL group. When these variables were compared with those of the other HIV-related NHL group, such differences were not present. CONCLUSION: Ki-1 ALCL is not a rare clinicopathologic entity among NHL in patients with HIV infection. The differences observed within the two Ki-1 ALCL groups of patients may be because of factors related to the HIV infection alone.

Adult↗
PubMed1995

Hodgkin's disease and human immunodeficiency virus infection: clinicopathologic and virologic features of 114 patients from the Italian Cooperative Group on AIDS and Tumors.

PURPOSE: To describe virologic, clinicopathologic, and therapeutic features of a large series of Italian patients with Hodgkin's disease (HD) and human immunodeficiency virus (HIV) infection. PATIENTS AND METHODS: From November 1986 to March 1994, 114 cases were observed. The relationship between Epstein-Barr virus (EBV) and HD was determined by an in situ hybridization technique, immunostaining for EBV-encoded latent membrane protein-1 (LMP-1) expression, and Southern blotting. Twenty-six patients were included in a prospective study evaluating the combination of chemotherapy (CT) with zidovudine. RESULTS: Combined approach on EBV study revealed that 14 (78%) of 18 patients were EBV-associated. An almost equivalent distribution of EBV subtypes was observed in EBV-carrying cases, indicating that in the HIV setting, type 2 EBV also may be pathogenetically involved in HD development. In comparing these 114 patients with our single-institutional series of 104 HIV-negative patients with HD, we observed at presentation a younger median age (29 v 38 years); a prevalence of males (90% v 56%); and a higher percentage of stage IV disease (52% v 15%), presence of B symptoms (77% v 35%), and extranodal disease (63% v 29%). The complete remission (CR) rate (58%) and median survival (13 months) of patients treated prospectively were similar to that of patients treated with standard CT regimens. The statistically significant favorable prognostic factors for survival being the following: achievement of CR, CD4+ count greater than 250/microL, and no prior diagnosis of AIDS at onset of HD. CONCLUSION: Our virologic findings indicate that HIV-related HD is more closely associated with EBV than HD in the general population. The peculiar clinicopathologic findings, the role of some prognostic factors, and the possibility of cure of HIV-related HD have been demonstrated.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Can a specifically-aimed pathologic classification overcome the difficulties in defining HIV-associated lymphomas?

High grade B-cell systemic lymphomas in HIV-infected patients exhibit pleomorphic features as well as some overlap between established histologic subtypes thus highlighting the difficulties in defining them precisely by making use of the classifications for non-Hodgkin's lymphomas (NHL) proposed before the AIDS epidemic. A series of HIV-associated systemic lymphomas including 114 NHL and 25 Hodgkin's disease (HD) cases were morphologically and immunopheno-genotypically investigated at the Centro di Riferimento Oncologico, Aviano, Italy during a period of nine years. The International Working Formulation (WF) for NHL, the updated Kiel Classification and, later, morphologic variants of high grade B-cell NHL have been adopted in order to obtain a more detailed and specific histopathologic description of HIV-associated lymphomas. As a consequence of morphologic data, and considering also pathogenetic aspects as derived from literature, we have attempted a pathological categorization of HIV-associated systemic lymphomas based on the recognition of two main groups: the "blastic" cell group and the "anaplastic" one, both including specific cytomorphologic subtypes with, possibly, aggressive HD subtypes within one of them. This categorization uses the WF, the updated Kiel system, and the morphologic variants of high-grade lymphomas, and provides a provisional category for cases with intermediate morphologic features. Thus other histologic subtypes, such as small noncleaved cell (Burkitt) and immunoblastic lymphomas, can be defined in a more accurate way. The clear-cut placement of "anaplastic" cell lymphomas, including anaplastic large cell (CD30/Ki-1+) lymphomas, including anaplastic large cell (CD30/Ki-1+) lymphomas and possibly a proportion of HD cases, emphasizes the need for their diagnostic differentiation from polymorphic "blastic"' cell lymphomas, immunoblastic ones in particular.

Humans↗
PubMed1995

CD40 ligand is constitutively expressed in a subset of T cell lymphomas and on the microenvironmental reactive T cells of follicular lymphomas and Hodgkin's disease.

Although CD40 has been extensively studied in B- and T-cell non-Hodgkin's lymphomas (NHLs)/leukemias, and more recently in Hodgkin's disease (HD), little is known about the expression of its ligand (CD40L) in lymphoproliferative disorders other than T-cell NHLs/leukemias. A series of 121 lymphoma/leukemia samples, including 35 cases of HD, 34 T-cell and 39 B-cells NHLs, 2 cases of adult T-cell leukemia/lymphoma, and 11 cases of T-cell acute lymphoblastic leukemia, were evaluated for CD40L expression by immunostaining of frozen tissue sections and flow cytometry with the anti-CD40L monoclonal antibody M90. CD40L was constitutively expressed by neoplastic cells in 15 of 36 (42%) T-cell NHLs/adult T-cell leukemia/lymphomas, almost invariably those displaying the CD4+/CD8- phenotype, whereas no CD40L-expressing tumor cells could be found in B-cell NHL and HD. Among T-cell acute lymphoblastic leukemias, CD40L was detected only on 2 cases displaying a stem-cell-like phenotype. In follicular B-cell lymphomas a large number of CD40L-expressing CD3+/CD4+ T lymphocytes were found admixed with tumor cells within the neoplastic follicles and in their surrounding areas. In the nonfollicular B-cell lymphomas, CD40L-positive CD3+/CD4+ T lymphocytes were few or absent. In all HD subtypes other than the nodular lymphocytic predominance, CD40L-expressing CD3+/CD4+ T lymphocytes were numerous in the HD-involved areas and were mainly located in close proximity to the Reed-Sternberg cells. Our data indicate that in human lymphomas CD40L is preferentially expressed by a restricted subset of T-cell lymphomas, mostly with CD4 immunophenotype. Finally, we have provided morphological evidence that CD40L may play an important role in the cell contact-dependent interaction of tumor B-cells (CD40+) within the neoplastic follicles or Reed-Sternberg cells (CD40+) in HD-involved areas and the microenvironmental CD3+/CD4+/CD40L+ T lymphocytes.

Adult↗
PubMed1995

Local cytokine expression in the progression toward B cell malignancy in Sjögren's syndrome.

OBJECTIVE: Sjögren's syndrome (SS) has been indicated as an ideal human model to investigate B cell lymphomagenesis. Our aim was to investigate similarities or differences in cytokine expression in both prelymphomatous and frank B cell lymphomatous SS lesions, as well as in SS related lesions versus SS unrelated malignant B cell non-Hodgkin's lymphomas. METHODS: The mRNA expression of interleukin (IL)-1 beta, IL-2, IL-3, IL-4, IL-6, IL-6R, IL-9, IL-10, IL-12, tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), and transforming growth factor beta (TGF-beta) was analyzed by a sensitive reverse transcriptase polymerase chain reaction technique in 10 SS tissue samples from 10 consecutive patients [7 nonmalignant parotid myoepithelial sialadenitis (MESA) lesions with evidence of B cell clonal expansion, and 3 B cell non-Hodgkin's lymphomas] as well as a series of 11 SS unrelated B cell non-Hodgkin's lymphomas. RESULTS: IL-1, IL-2, IL-3, IL-6, IL-6R, IL-10, IL-12, IFN-gamma, TNF-alpha, and TGF-beta mRNA was expressed in all or in the vast majority of the samples analyzed. IL-4 mRNA was detected in 2/3 SS related and in 3/11 SS unrelated non-Hodgkin's lymphomas, while SS related MESA samples were characterized by an IL-4 negative pattern and lacked IL-3 or IFN-gamma expression in 3/7 cases and in 2/7 cases, respectively. CONCLUSION: Many cytokines may be involved in the evolution of prelymphomatous to definite B cell malignant lesions in SS, as well as in the development of SS unrelated B cell non-Hodgkin's lymphomas. A putative pathobiological role of the IL-12/IL-4 balance, in the presence of cytokines that may sustain B cell proliferation (i.e., IL-3, IL-6, IL-10), may represent a major point for future research. Finally, our data reinforce the view of SS as a human model of B cell lymphomagenesis.

Adult↗
PubMed1995

[Recent insights on the pathogenesis of non-Hodgkin's lymphoma].

Molecular pathology findings that are related to lymphomagenesis may be used as diagnostic tools, in conjunction with conventional methods. In particular, the use of genetic lesions as diagnostic markers of non-Hodgkin's lymphomas is supported by the selective association of certain genetic alterations with specific histological entities.

Biomarkers, Tumor↗
PubMed1994

Molecular mechanisms possibly affecting WT1 function in human ovarian tumors.

The frequent allelic deletions observed on the short arm of chromosome 11 in ovarian tumors suggest that the WT1 gene, a proposed tumor-suppressor gene located on chromosome 11p13 and expressed in the human fetal genitourinary system, may contribute to the development of ovarian neoplasms. Structural and sequence analysis of the entire coding portions of the WT1 gene did not reveal any abnormalities in the 20 ovarian tumor specimens (13 of which showed 11p13 allelic deletions) and 5 cell lines which we analyzed. These findings invalidate the hypothesis that the WT1 gene functions as a classical tumor-suppressor gene in ovarian tumorigenesis and suggest that a different recessive oncogene may be "exposed" by the observed 11p13 allelic deletions. Expression analysis showed that the WT1 gene was transcriptionally active in all the tumors tested, but considerable variations in the mRNA levels were found. This apparent variability, which should be confirmed at the cellular level in the tumor specimens, was also observed in the ovarian tumor-cell lines. Finally, WT1 expression data were evaluated in conjunction with immunohistochemical data on p53. The possible functional effects of altered WT1 mRNA expression in ovarian tumors are discussed, taking into account the potential WT1/p53 protein interaction.

Adenocarcinoma↗
PubMed1994

p53 protein over-expression and p53 gene abnormalities in HIV-1-related non-Hodgkin's lymphomas.

Alteration of the p53 tumor-suppressor gene was studied in non-Hodgkin's lymphomas (NHLs) from HIV-1-infected patients. p53 protein was over-expressed in 10 out of the 45 (22%) cases analyzed, mainly clustering in the small-non-cleaved-cell (SNC) (5/19) and Ki-1+ anaplastic large-cell (ALC) (3/8) sub-types, according to previous findings on HIV-1-unrelated NHLs. p53-positive small-non-cleaved-cell lymphomas presented a diffuse or clustered pattern of p53-positive neoplastic cells consequent upon p53-gene mutations. In contrast, in Ki-1+ ALC lymphomas p53 immunohistochemical reactivity was limited to scattered tumor cells, and no p53-gene alterations could be detected. These results suggest that p53-gene alterations play a role in the lymphomagenetic process of a fraction of HIV-1-related SNC NHLs, however with a frequency no different from that observed in HIV-1-unrelated NHLs of the same sub-type. In HIV-1-related Ki-1+ ALC lymphomas, mechanisms different from gene alterations might be implicated in over-expression of p53 protein.

Base Sequence↗
PubMed1994

Expression of the c-kit receptor in human lymphomas is restricted to Hodgkin's disease and CD30+ anaplastic large cell lymphomas.

The product of the proto-oncogene c-kit is a transmembrane receptor protein that plays an important role in the regulation of normal and neoplastic hematopoiesis via the interaction with its specific ligand termed stem cell factor. To examine whether c-kit product is possibly involved in the pathogenesis of human lymphomas, we analyzed the expression of the c-kit protein in neoplastic cells from a variety of lymphoid tumors by immunostaining of lymph node frozen sections with the 17F11 antibody, detecting an extracellular epitope of the c-kit receptor, and of c-kit RNA by Northern blot hybridization. Of 24 nonHodgkin's lymphomas (NHL) of B- and T-cell phenotype, none expressed immunodetectable c-kit protein that was also not evidenced in lymphoid cells of reactive lymph nodes and normal tonsils. In contrast, c-kit protein was expressed by Reed-Sternberg cells and their mononuclear variants from 11 of 21 Hodgkin's disease (HD) cases, and in tumor cells from 11 of 16 cases of CD30+ anaplastic large cell lymphoma (ALCL). c-kit specific mRNA was also detected in lymph node tissues from HD and ALCL cases but not in neoplastic tissues from NHL other than ALCL. In addition, c-kit/CD30+ tumor cells were evidenced by flow cytometry in a patient displaying massive bone marrow involvement by ALCL. With the exclusion of lymphocyte predominance cases of HD that resulted c-kit expression and the other histologic subtypes of HD or the immunologic phenotype of tumor cells (B, T, nonB-nonT) in both HD and ALCL. The highly restricted expression of the c-kit product among human lymphomas to HD and ALCL provides a further biologic link between these two closely related lymphoma entities.

Hodgkin Disease↗