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A Gloghini

Publications and source records attributed to A Gloghini.

At least 109 records · Page 6Linked to original sources
PubMed1996

AIDS-related non-Hodgkin's lymphomas: molecular genetics, viral infection and cytokine deregulation.

AIDS-related non-Hodgkin's lymphomas (AIDS-NHLs) are almost invariably derived from B cells and are grouped into three distinct histologic categories, including small-non-cleaved-cell lymphoma (SNCCL), diffuse large-cell lymphoma (DLCL), and anaplastic large-cell lymphoma (ALCL). In addition, AIDS-NHLs presenting solely as a body cavity effusion are thought to be a peculiar clinicopathologic entity and are defined as body-cavity-based lymphoma (BCBL). At the biologic level, AIDS-related lymphomagenesis is characterized by activation of proto-oncogenes, inactivation of tumor suppressor genes, viral infection of the tumor clone, and deregulated cytokine production. Distinct AIDS-NHL types associate with specific molecular pathways. The first pathogenetic pathway clusters with AIDS-SNCCL, and is characterized by a relatively mild degree of host immunodeficiency. AIDS-SNCCL consistently associates with c-myc rearrangements and p53 inactivation in 100 and 60% of cases, respectively, whereas infection by Epstein-Barr virus (EBV) is restricted to 30% of the cases. Production of high levels of interleukin-10 is an additional peculiar feature of EBV-positive AIDS-SNCCL. The second pathogenetic pathway associates with AIDS-DLCL, which is usually accompanied by marked host immunodeficiency. AIDS-DLCL is characterized by EBV infection in the large majority of cases and by the mutually exclusive presence of bcl-6 rearrangements and c-myc translocations in 40% of the cases. A third pathway characterizes AIDS-BCBL, which associates in virtually all cases with infection by EBV and with the presence of DNA sequences of the recently identified Kaposi sarcoma herpesvirus in the apparent absence of other known genetic lesions. Finally, the pathogenetic features of AIDS-ALCL are still under investigation.

Cytokines↗
PubMed1996

Morphologic patterns and molecular pathways of AIDS-related head and neck and other systemic lymphomas.

Head and neck manifestations of human immunodeficiency virus (HIV) infection include lymph nodal and extranodal localization of non-Hodgkin's lymphoma (NHL). A histopathologic characteristic common to head and neck NHLs and to all the other systemic lymphomas in HIV patients is the frequent occurrence of cases displaying pleomorphic features and some overlap between established histologic subtypes. This article highlights the difficulties in defining HIV-related NHLs correctly, and proposes a specific pathologic categorization of these disorders accounting for their pathogenic aspects as gathered from molecular data.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Hodgkin's disease: old and recent clinical concepts.

The diagnosis of Hodgkin's disease (HD) is still primarily based on the histopathologic criteria presented by Lukes et al in 1965. Over the past three decades, however, advances in immunohistochemistry, molecular studies, and virologic findings have provided evidence that HD exhibits significant heterogeneity. Whereas the nodular sclerosis subtype is the major subset of the "classic" disease, it has become evident that the nodular, lymphocytic predominance subtype may represent a minor distinct subset, and possibly a distinct disease entity. Furthermore, there is strong evidence that the mixed cellularity subtype may be an Epstein-Barr virus-related disorder. Finally, based on phenotypic and genotypic features, the existence of a "continuum" between a fraction of HD cases, including the lymphocytic depletion subtype, and CD30-positive anaplastic large cell lymphomas has been suggested.

HIV Infections↗
PubMed1996

Malignant lymphomas in patients with HIV infection.

During the last two decades, the occurrence of non-Hodgkin's lymphoma (NHLs) has been increasing both in the general population, in which their incidence doubled, and in people with human immunodeficiency virus (HIV) infection, in whom a 100-fold increase has been observed since the onset of the AIDS epidemic. HIV infected patients are living longer owing to advances in antiretroviral therapy and treatment of prophylaxis against opportunistic infections but because of their immunodeficiency they are at high risk of cancers, especially NHL. The natural history of cancers in patients with HIV infection differs from that of the general population. Unusual aspects of tumor localization, growth behaviour and therapeutical response, distinguish tumors in patients with from those without HIV infection. The pathologic and virological aspects of HIV-related tumors are peculiar and a pathological classification of HIV associated systemic lymphomas based on the morphological features of the two main types, i.e. blastic and anaplastic cell lymphomas has been formulated. The treatment of HIV-related neoplasms is controversial as it is not clear whether conventional therapy and in particular chemotherapy is able to modify the natural history of these malignancies in HIV setting. Moreover the treatment of HIV-related tumors presents several problems, due to the aggressive behaviours of tumors and because of immunosuppressive chemotherapy employed in patients with immunodeficiency.

Humans↗
PubMed1996

Association of 6q deletions with AIDS-related diffuse large cell lymphoma.

Deletions of chromosome 6 at band q27 represent the site of a putative novel tumor suppressor gene in non-Hodgkin's lymphomas (NHL) of the immunocompetent host. Although several genetic lesions have been identified in AIDS-related NHL (AIDS-NHL), the involvement of 6q27 loss has not been investigated in this NHL category. In this report, we tested the presence of a 6q deletion at the molecular level in a panel of AIDS-NHL representative of the major histologic types, including AIDS-related small non-cleaved cell lymphoma (AIDS-SNCCL; n = 10), AIDS-related diffuse large cell lymphoma (AIDS-DLCL; n = 13) and AIDS-related anaplastic large cell lymphoma (AIDS-ALCL; n = 3). We report that 6q deletions occur in 5/26 AIDS-NHL tested (19.2%). Notably, 6q deletions do not randomly distribute throughout the spectrum of AIDS-NHL histologic types, but rather selectively cluster with AIDS-DLCL (5/13; 38.4%). Overall, these data add to the notion that the molecular pathogenesis of AIDS-NHL is heterogeneous and that distinct genetic pathways associate with specific histologic categories of AIDS-NHL.

Blotting, Southern↗
PubMed1996

CD30 ligand expression in nonmalignant and Hodgkin's disease-involved lymphoid tissues.

The CD30 ligand (CD30L) is a type II transmembrane glycoprotein of the tumor necrosis factor ligand superfamily. Recent cloning of CD30L has enabled studies to explore its function and tissue distribution. For instance, recombinant CD30L has been shown to co-stimulate T cells and to act as mitogen for Hodgkin's disease (HD)-derived cell lines. The counter-receptor for CD30L, ie, CD30, is a type I cytokine receptor that is highly expressed by activated T cells, Hodgkin and Reed-Sternberg (H-RS) cells, and anaplastic large cell lymphoma cells. In the present study, recombinant membrane-bound and soluble human CD30L were instrumental to raise a monoclonal antibody (M80) recognizing membrane-bound CD30L on transfected and native cells. With this reagent, a panel of cultured lymphoma-derived cell lines as well as primary normal, reactive, and HD-involved lymphoid tissues were examined for expression of CD30L by immunostaining and flow cytometry. In reactive lymphnodes and tonsils, CD30L was expressed by a small subset of lymphoid cells, histiocytes, and granulocytes. Higher levels of CD30L expression were noted in HD lesions among bystander cells; ie, T cells and granulocytes that surrounded H-RS cells. Native CD30L displayed at the cell surface was functionally active as shown by the ability of fixed granulocytes to interact with CD30+ cell lines. Moreover, CD30L was detectable, although to a lower staining intensity, in primary H-RS cells of all HD tissues investigated regardless of the histological subtype and the phenotype of H-RS cells (ie, CD30+/CD40+ versus CD30-/CD40+). Co-expression of CD30 and CD30L that was seen on H-RS cells of all, except the CD30- nodular lymphocyte predominant, subtypes of HD may point to the use of this pair of molecules in paracrine and/or autocrine mitogenic cell interactions. Monoclonal antibody M80 may thus represent a useful tool for studying CD30L expression on cultured cell lines and primary cells from normal, reactive, and malignant tissues.

Antibodies, Monoclonal↗
PubMed1996

The role of current and new discriminating markers in the immunodiagnosis of Hodgkin's disease and other phenotypically related lymphomas.

Recent data have shown that CD40 antigen and its ligand (CD40L), and the CD26 molecule are differentially expressed among Hodgkin's disease (HD) (CD40+, CD26, CD40L), peripheral T-cell (PTCL) (CD40L+/-, CD40, CD26) and CD30 positive anaplastic large cell (ALC) (CD26+, CD40L) lymphomas. Since CD40 molecule is consistently detected on Reed-Sternberg (RS) cells and their morphologic variants with a distinctive staining pattern. CD40 expression provides a new potential tool for the identification of RS cells of HD in fixed and paraffin-embedded material. Furthermore, the combined application of anti-CD40 and anti-CD26 MoAbs may discriminate HD from morphologically and immunophenotypically related ALC lymphomas. In fact a CD26+/CD40 profile is restricted to CD30 positive ALC lymphomas. Finally, the combined application of anti-CD40 and anti-CD40L MoAbs provides additional significant features in differentiating HD from PTCL due to the constant expression of CD40+/CD40L phenotype in HD and its absence in PTCL, which in turn express CD40/CD40L+/- phenotype.

Antigens, CD↗
PubMed1995

The expression of CD26 and CD40 ligand is mutually exclusive in human T-cell non-Hodgkin's lymphomas/leukemias.

CD26 and CD40 ligand (CD40L) are surface molecules on human activated T lymphocytes that play a critical role in the regulation of lymphopoiesis. Both molecules are expressed on a restricted fraction of human T-cell non-Hodgkin's lymphomas (NHL)/leukemias; however, little is known about their functional and/or clinical significance in these disorders. In this study, the pattern of expression of CD40L was compared with that of the CD26 molecule. A series of 67 human T-cell NHL/leukemias and a panel of leukemia/lymphoma T-cell lines were evaluated by immunohistochemistry, flow cytometry, and RNA studies. The overall frequency of CD26+ and CD40L+ samples was rather similar (25/67 [37%] v 18/67 [27%]). However, the majority of CD26-expressing cases clustered in the lymphoblastic lymphomas (LBL)/T-acute lymphoblastic leukemias (ALL; 12/23) and CD30+ anaplastic large-cell (ALC) lymphomas (5/8), whereas CD40L+ lymphomas included a large fraction of mycosis fungoides (11/21 [52%]). CD26 and CD40L coexpression was found only in 2 myocosis fungoides cases and 1 small lymphocytic lymphoma. Thus, the expression of the two antigens was mutually exclusive in almost all T-cell lymphomas/leukemias. Accordingly, lymphoma cell lines expressed either one of the molecules or the relative amounts of CD26 and CD40L were inversely proportional. In contrast, reactive T lymphocytes from patients with non-neoplastic T-cell expansions and in vitro activated CD3+ or CD4+ normal T cells were found to coexpress CD40L and CD26. Results of a multivariate analysis showed that the expression of CD26 in T-cell LBL/ALL patients was associated to a worse outcome in terms of survival, as compared with patients with CD26- tumors (P < or = .0001). Based on our results, it can be concluded that, (1) as opposed to activated or reactive normal T cells, the expression of CD26 and of CD40L is mutually exclusive in human T-cell lymphomas/leukemias; (2) expression of CD26 is restricted to aggressive pathologic entities, such as T-cell LBL/ALL and T-cell CD30+ ALC lymphomas, whereas CD40L is expressed on slow progressing diseases such as mycosis fungoides; and (3) within the T-cell LBL/ALL group of tumors, CD26 may identify a subset of poor prognosis patients.

Adolescent↗
PubMed1995

Characteristics of EBV-infected cells in HIV-related lymphadenopathy: implications for the pathogenesis of EBV-associated and EBV-unrelated lymphomas of HIV-seropositive individuals.

The present study was performed with the aim of better defining the possible role of Epstein-Barr-virus (EBV)-infected cells in the pathogenesis of HIV-related lymphadenopathy syndrome (LAS). In addition, since LAS has been considered as a pre-lymphomatous lesion, we also wished to elucidate the possible contribution of EBV-carrying cells present in LAS tissues to the development of HIV-associated malignant lymphomas. To this end, we have characterized EBV-infected cells in LAS lymph nodes in terms of EBV DNA prevalence, tissue distribution in relation to HIV-carrying cells, virus sub-type, expression of latent and replicative antigens, and presence of clonal EBV episomes. When compared with HIV-unrelated lymphadenopathies (4/10, 40%), LAS showed a higher prevalence of EBV DNA (14/20, 70%). Comparable values of EBV prevalence were detected in LAS with follicular hyperplasia (12/16, 75%) and with follicular involution (4/4, 100%). All EBV+ non-neoplastic lymph nodes from HIV-seronegative patients carried type-I EBV, whereas LAS specimens showed almost equivalent distribution of the 2 EBV sub-types. Of the 14 EBV-carrying LAS, 4 (29%) were positive by Southern-blot analysis for the BamHI-W region of the virus genome but negative for the presence of monoclonal EBV episomes. In situ hybridization revealed a remarkably higher load of EBV-infected cells in LAS than in HIV-unrelated lymphadenopathies. In LAS lymph nodes, EBV-carrying cells were identified as isolated, cytologically normal elements, sometimes with immunoblastic morphology, usually scattered throughout the interfollicular areas. By contrast, the expression of HIV p24 was restricted to germinal center cells. All the EBV+ LAS samples were negative for the expression of EBV-encoded latent (LMP-1 and EBNA-2) and replicative proteins (BZLF-1, BHLF-1, EA-D, EA-R and VCA). In addition, amplification of the immunoglobulin heavy-chain genes using 2 different polymerase-chain-reaction protocols showed evidence of B-cell clonal expansion in 2/20 (10%) LAS, one EBV- case, and one sample with low numbers of EBV-infected cells. These results suggest that (i) EBV-carrying cells are probably not involved in the development of LAS, either directly or indirectly; (ii) type-2-EBV-infected cells are present in LAS lymph nodes from the early phases of HIV infection; (iii) EBV-carrying LAS per se probably does not constitute a lesion at high risk for subsequent development of EBV+ lymphomas; (iv) it is unlikely that a high viral load or strong EBV-mediated antigenic stimulation plays a contributory role in the development of EBV-unrelated lymphomas of HIV-seropositive individuals.

AIDS-Related Complex↗
PubMed1995

Hepatitis C virus within a malignant lymphoma lesion in the course of type II mixed cryoglobulinemia.

Hepatitis C virus (HCV) has been implicated as the major etiologic factor sustaining B-cell clonal expansion in type II mixed cryoglobulinemia (MC). A putative pathogenetic role of HCV in the development of MC-associated B-cell malignancies has also been speculated. We report for the first time the localization of HCV within a parotid non-Hodgkin's lymphoma (NHL) lesion in the course of HCV-related type II essential MC, an important step to implicate any infectious agent in the lymphomagenesis. Plus and minus strand HCV RNA was first demonstrated by polymerase chain reaction on the whole RNA from the lesion. Further immunohistochemical studies localized HCV c22 proteins in the residual ductal or acinar parotid structures, which also abnormally expressed HLA-DR antigens. Weak c22 signals were inconstantly detected in cells strictly confined around the residual epithelium, while all the remaining infiltrating cells in the parotid lesion stained c-22-negative. Staining for c33 and c100 HCV antigens was negative. In situ hybridization (ISH) studies again identified the residual parotid epithelial cells as the site of HCV infection and replication in the NHL lesion. Sialotropic viruses previously involved in lymphoproliferation, ie, Epstein-Barr virus and human herpesvirus-6, were absent in the same tissue lesion. According to the current models of B-cell lymphomagenesis, a role of HCV as an exogenous antigenic stimulus should be considered for NHL development in the present case, whereas malignant B cells do not appear permissive of active HCV replication. Further efforts would be worthwhile to clarify a role of HCV infection in the development of some B-cell malignancies.

Aged↗
PubMed1995

Identification and characterization of an Epstein-Barr virus-specific T-cell response in the pathologic tissue of a patient with Hodgkin's disease.

Several lines of evidence indicate that an impairment of EBV-specific immune responses may contribute to the pathogenesis of Hodgkin's disease (HD). At present, however, it is not clear whether a defective immunity to EBV is a characteristic restricted to EBV-associated HD cases or a more generalized phenomenon, part of the inherent immune deficiency of HD patients. In this study, we have addressed this issue by analyzing EBV-specific responses in infiltrating T lymphocytes (TILs) from one HD biopsy, where the virus was confined to a small proportion of apparently normal lymphocytes. TIL cultures were established using low amounts of recombinant interleukin 2 and in the absence of specific stimulation, conditions that preferentially induce the proliferation of in vivo activated T cells. An EBV-specific cytotoxic component was revealed by the capacity of these TILs to lyse autologous EBV-positive lymphoblastoid cell lines (LCLs) obtained by spontaneous transformation from the lesion but not HLA-mismatched LCLs and autologous phytohemagglutinin blasts. This cytotoxic activity closely resembled that of EBV-specific memory T cells, which may be reactivated from the blood lymphocytes of healthy donors by in vitro stimulation with autologous LCLs. The use of a panel of appropriately HLA-matched B95.8-transformed LCLs as targets in standard 51Cr release assays revealed EBV-specific cytotoxic responses to be restricted mainly through the A11 and B44 HLA alleles with a minor HLA-A26-restricted component. Using autologous fibroblasts infected with recombinant vaccinia viruses expressing the EBV latent antigens, the TIL culture was shown to recognize latent membrane protein 2 and, to a lesser extent, EBV-encoded nuclear antigen 6. In addition, a strong proliferative response was induced by coculture of TILs with autologous but not with allogeneic LCLs or autologous phytohemagglutinin blasts. Six CD4-positive, EBV-specific T-cell clones were isolated by limiting dilution. The study of cytokine mRNA expression, carried out by reverse transcriptase-assisted PCR, revealed that three of these T-cell clones expressed a Th0 phenotype, whereas 1 had a Th2 phenotype. These findings are consistent with the presence in this HD lesion of an ongoing immune response against EBV-carrying cells and suggest that the complex immune deficiency that characterizes HD patients probably does not include a generalized, constitutional defect of EBV-specific T-cell responses.

Adult↗
PubMed1995

MDM2 overexpression does not account for stabilization of wild-type p53 protein in non-Hodgkin's lymphomas.

p53 protein overexpression is a frequent finding in non-Hodgkin's lymphomas (NHL), being detected in over 25% of the cases. Moreover, some high-grade lymphomas and a large fraction of low-grade tumors show a pattern of scattered p53 accumulation in a limited percentage of neoplastic cells. In contrast, NHLs show a low frequency of p53 gene mutations. To investigate the molecular bases of p53 protein overexpression, a large series of NHLs was analyzed for p53 gene status. The analysis of the entire coding region of the gene (exons 2-11) and corresponding donor and acceptor splicing sites indicated that a significant proportion of p53-positive tumors overexpresses a wild-type form of p53 protein (wt-p53). To assess whether wt-p53 accumulation was related to the formation of inactive complexes with endogenous proteins, MDM2 oncogene expression and amplification were analyzed. MDM2 overexpression was detected only in one third of the wt-p53-positive cases, thus excluding that MDM2 accounts tout court for the accumulation of a normal p53 protein. However, the fact that MDM2 overexpression was detected in only the p53-positive cases and the observation that MDM2-positive cells were a subpopulation of p53-positive cells suggest a link between the two phenomena. In particular, our results indicate that the accumulation of a wt form of p53 protein could promote the overexpression of the MDM2 gene product. In addition, the prevalence of MDM2 positivity in intermediate/high-grade tumors together with the concordant expression of wt-p53 and MDM2 only in the high-grade component of a 'composite' lymphoma suggests that perturbation in the MDM2/p53 critical ratio could play a role in lymphoma progression.

Base Sequence↗
PubMed1995

Expression of protectin (CD59) in human melanoma and its functional role in cell- and complement-mediated cytotoxicity.

Immunohistochemical and/or indirect immunofluorescence analysis with monoclonal antibody (MAb) H19 demonstrated the expression of protectin (CD59) in 54 surgically removed metastatic melanoma lesions and on 8 out of 12 melanoma cell lines. CD59 expression had a low degree of intra- and intertumor heterogeneity. SDS-PAGE analysis showed that the molecular weight of CD59 expressed on melanoma cells is about 20 kDa. Treatment of melanoma cells with 5U/ml of phosphatidylinositol-specific phospholipase C completely abolished cell-surface expression of CD59. Interferon-gamma and/or tumor necrosis factor-alpha or phorbol 12-myristate 13-acetate neither modulated the expression of CD59 by melanoma cells nor influenced the amounts of CD59-specific mRNA. F(ab')2 fragments of anti-CD59 MAb YTH53. I did not inhibit the lysis of melanoma cells by allogeneic natural killer (NK) cells or lymphokine-activated killer (LAK) cells. In contrast, the whole Ig molecule of MAb HI9 or YTH53.I significantly (p < 0.05) enhanced NK-cell-mediated lysis of melanoma cells, suggesting the induction of antibody-dependent cell-mediated cytotoxicity. Lastly, masking of CD59 by MAb YTH53.I or its F(ab')2 fragments significantly (p < 0.05) enhanced, in a dose-dependent fashion, the lysis of anti-GD3-sensitized melanoma cells by homologous complement. These data demonstrate that CD59 expressed by human melanoma cells might regulate host-tumor interaction by protecting neoplastic cells from complement-mediated lysis.

Antibodies, Monoclonal↗
PubMed1995

High frequency of EBV association with non-random abnormalities of the chromosome region 1q21-25 in AIDS-related Burkitt's lymphoma-derived cell lines.

Chromosome 1q abnormalities represent the second most frequent cytogenetic lesion of Burkitt lymphoma (BL) and acute lymphoblastic leukemia (ALL)-L3. The most frequent change is partial duplication of the long arm of chromosome 1, involving variable bands but consistently including 1q23. Among AIDS-related BL similar chromosome 1q abnormalities have also been found. We have now characterized in detail the chromosome 1q abnormalities of 4 AIDS-BL cell lines and compared them to other molecular features of the tumor clone, namely infection by Epstein Barr virus (EBV). Immunophenotypic characteristics were also assessed by conventional in situ immunocytochemical and flow cytometric procedures. The B-cell origin of all cell lines was demonstrated by the expression of B-cell-restricted markers (e.g., CD19). Analysis of Ig light chains confirmed their monoclonal nature. The t(8;14) was present in 3 of the 4 lines, whereas variant translocation t(8;22) was detected in the remaining cell line. Additional chromosomal changes were found in all cases, with chromosome 1 being involved in all. Structural changes encompassed in each case the 1q21-25 bands, in either duplication or partial trisomy. EBER ISH studies identified EBV association in 3 of the 4 AIDS-BL cell lines in contrast to previous studies of BL of immunocompetent individuals. Our findings of a high frequency of chromosome 1q abnormalities in EBV-infected AIDS-related BL cell lines demonstrate that such chromosomal abnormality and EBV positivity are not mutually exclusive and are possibly independent factors, whereas their close association in AIDS may be related to the immunodeficiency.

Burkitt Lymphoma↗
PubMed1995

Analysis of the p53 gene in relation to tobacco and alcohol in cancers of the upper aero-digestive tract.

To elucidate the relationship, if any, of p53 gene expression according to smoking and drinking habits, 135 subjects with cancer of the upper aero-digestive tract were sampled from a case-control investigation conducted in Pordenone province, Northeast Italy, between 1986 and 1991. Adequate pathological material for immunohistochemical analysis was available for 83 subjects. Level of p53 expression was classified according to intensity on immunoreaction and percentage of p53-positive cells. Mutations were analyzed by means of single-strand conformation polymorphism and sequencing in 8 p53-positive life-long non-smokers exposed to various levels of alcohol intake. The association between p53 expression and smoking status and alcohol intake was evaluated by means of odds ratios, and 95% confidence intervals. Significantly, more men (39/65) than women (6/18) had elevated p53 expression. No significant trend of increasing percentage of p53-positive cancers with increasing smoking and drinking level was detected, especially after allowance for gender. With respect to specific mutation pattern, in 8 life-long non smokers who drank alcohol, 6 mutations involved G:C base pairs. G-to-A transitions were identified in 4 cases. The present study does not support an association between elevated p53 expression and tobacco smoking or alcohol intake. It provides an example of a molecular biology study in the framework of a large epidemiological investigation.

Aged↗
PubMed1995

Expression of functional CD40 antigen on Reed-Sternberg cells and Hodgkin's disease cell lines.

CD40 is a member of the nerve growth factor receptor family, showing a significant homology to the Hodgkin's disease (HD)-associated antigen CD30 and is capable of transduce growth signals in a number of cell types. A series of 312 lymphoma samples, including 139 cases of HD, 32 cases of CD30+ anaplastic large cell (ALC) lymphomas, 141 cases of other non-Hodgkin's lymphomas (NHLs), and a panel of HD- or NHL-derived cell lines, were evaluated for CD40 expression by immunostaining of paraffin embedded sections, cell smears and flow cytometry. CD40 was strongly expressed with a highly distinct pattern of staining on Reed-Sternberg (RS) cells and variants in 100% (139/139) of HD cases, irrespective of their antigenic phenotype (T, B, non T-non B) and histologic subtype of HD. Conversely, CD40 was immunodetected on only one third (12/32; 37%) of ALC lymphoma cases and on 105 of 127 B-cell NHLs. The relative cell density of CD40 on HD cell lines (L-428, KM-H2, HDLM-2) as assessed by flow cytometry was significantly higher than on all other lymphoma cells analyzed. Engagement of CD40 by its soluble ligand (CD40L) enhanced both clonogenic capacity and colony cell survival of HD cell lines. Such effect was potentiated by interleukin-9 costimulation in KM-H2 cells. Finally, we have shown that in vitro rosetting of activated CD4+ T cells to HD cells (L-428) is mediated in part by the CD40/CD40L adhesion pathway. Our data indicate that CD40 is a useful antigen for immunodetection and identification of tumor cells in all subtypes of HD, and suggest that it may play a role in the regulation of RS cell expansion and the contact-dependent interactions of these cells with cytokine-producing T lymphocytes.

Animals↗
PubMed1995

Head and neck lymphomas associated with human immunodeficiency virus infection.

OBJECTIVE: To focus on clinicopathologic data of non-Hodgkin's lymphomas (NHLs) of the head and neck area (with lymph nodal or extranodal localization) arising in patients with immunodeficiency virus (HIV) infection. PATIENTS: Among 73 evaluable patients for presenting symptoms, of a total of 82 with HIV-related NHLs whose conditions were diagnosed at the Centro di Riferimento Oncologico, Aviano (Italy), between September 1984 and May 1992, 15 (21%) had primary, solitary head and neck (P-HN) lymphoma and 13 (18%) had systemic head and neck (S-HN) lymphoma arising from this region. RESULTS: Ten (67%) of 15 patients with P-HN NHL had stages I and II, whereas all patients with S-HN NHL had stages III and IV. Twenty-seven of 28 patients had extranodal disease at presentation, the principal sites being Waldeyer's ring and soft tissues. There were only high-grade (14 cases) or intermediate-grade (three cases) NHLs, the most frequent histotypes being small noncleaved cell, Burkitt's type, and large-cell immunoblastic. Seven of 11 cases in the miscellaneous group of the working formulation were classified as Ki-1+ anaplastic large-cell lymphoma. By immunophenotypic and genotypic characterization, a B-cell derivation was suggested for 21 of 28 NHLs. After combination chemotherapy with or without radiotherapy, a complete remission was observed in seven (58%) of 12 patients with P-HN lymphoma and in only two patients with S-HN lymphoma. Median survival was 9.8 months for the patients with P-HN lymphoma and 8.3 months for the other patients. Thirteen patients died, the most common causes of death being opportunistic infections (five cases) and progression of lymphoma (four cases). CONCLUSIONS: Most HIV-infected patients with head and neck NHL had severe immunodeficiency, extranodal disease, aggressive histologic findings, and a poor treatment response.

Adult↗