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Biomedical subjects

M F d'Agay

Publications and source records attributed to M F d'Agay.

At least 19 recordsLinked to original sources
PubMed1996

Prognostic significance of bcl-2 protein expression in aggressive non-Hodgkin's lymphoma. Groupe d'Etude des Lymphomes de l'Adulte (GELA).

Little is known about the expression of bcl-2 protein in intermediate and high grade non-Hodgkin's lymphoma (NHL) and its clinical and prognostic significance. We performed immunohistochemical analysis of bcl-2 expression in tumoral tissue sections of 348 patients with high or intermediate grade NHL. These patients were uniformly treated with adriamycin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) in the induction phase of the LNH87 protocol. Fifty eight cases were excluded due to inadequate staining. Of the 290 remaining patients, 131 (45%) disclosed homogeneous positivity (high bcl-2 expression) in virtually all tumor cells, whereas 65 (23%) were negative and 94 (32%) exhibited intermediate staining. High bcl-2 expression was more frequent in B-cell NHL (109 of 214, 51%) than in T-cell NHL (6 of 35, 17%) (P = .0004), and was heterogeneously distributed among the different histological subtypes. Further analysis was performed on the 151 patients with diffuse large B-cell lymphoma (centroblastic and immunoblastic) to assess the clinical significance and potential prognostic value of bcl-2 expression in the most frequent and homogeneous immunohistological subgroup. High bcl-2 expression, found in 44% of these patients (67 of 151), was more frequently associated with III-IV stage disease (P = .002). Reduced disease-free survival (DFS) (P < .01) and overall survival (P < .05) were demonstrated in the patients with high bcl-2 expression. Indeed, the 3-year estimates of DFS and overall survival were 60% and 61%, respectively (high bcl-2 expression) versus 82% and 78%, respectively (negative/intermediate bcl-2 expression). A multivariate regression analysis confirmed the independent effect of bcl-2 protein expression on DFS. Thus bcl-2 protein expression, as demonstrated in routinely paraffin-embedded tissue, appears to be predictive of poor DFS, in agreement with the role of bcl-2 in chemotherapy-induced apoptosis. It might be considered as a new independent biologic prognostic parameter, which, especially in diffuse large B-cell NHL, could aid in the identification of patient risk groups.

Adult↗
PubMed1996

Primary mediastinal large B-cell lymphoma. A clinicopathologic study of 141 cases compared with 916 nonmediastinal large B-cell lymphomas, a GELA ("Groupe d'Etude des Lymphomes de l'Adulte") study.

Among non-Hodgkin's lymphomas, primary mediastinal large B-cell lymphoma (PMLCL) has been considered a separate entity that has specific clinical and histological aspects and a poor prognosis. In this study, we reexamined the clinicopathologic features and the response to current treatment of 141 PMLCL and compare them with 916 nonmediastinal large B-cell lymphomas (NMLCL) recorded in the same period and treated with similar combined chemotherapy. The clinical features of PMLCL at diagnosis were largely homogeneous and distinct from NMLCL, with a predilection for young women (59% with a mean age of 37 years versus 42% with a mean age of 54 years), bulky tumor (77% versus 7%, p < 10(4)), high serum lactic dehydrogenase (LDH) level 76% versus 51%, p < 10(4)), and frequent intrathoracic extension to adjacent organs such as pleura, pericardium, and lung. By contrast, extrathoracic or hematologic dissemination was uncommon (2% of bone marrow involvement versus 17%). All patients had diffuse large B-cell nonimmunoblastic, nonanaplastic lymphomas. Histological analysis of the 141 PMLCL evaluated two common patterns: the presence of large cells with clear cytoplasm (found in 38% of cases) and the presence of fibrosis (marked in 25% of cases). The presence of clear cells or intense fibrosis did not constitute prognostic indicators. Immunologic and molecular analysis assessed the profile of bcl-2 expression and the presence of Epstein-Barr virus (EBV) in PMLCL: 30% expressed a high level of bcl-2 protein; EBER RNAs were detected by in situ hybridization in only two of the 41 cases tested. Monotypic light chain restriction could be demonstrated in seven of the 41 PMLCL tested on fixed-section. Treated with polychemotherapy regimens without radiotherapy, 79% of PMLCL patients achieved a complete remission compared with 68% in the NMLCL patient group (p = 0.01). Overall, 3-year survival rates were estimated at 66 and 61%, respectively (p = 0.05), and disease-free survival rates were not significantly different (61 versus 64%). Stratified analysis on the International Prognostic Index (based on age, tumor stage, serum LDH level, and performance status) showed no difference in the overall and disease-free survivals between the two lymphoma groups. In conclusion, PMLCL can be combined with other diffuse large B-cell lymphomas on morphologic grounds; it is not associated with EBV. It responds favorably to treatment and should be managed like other high-grade lymphomas of equivalent histology. However, the uncommon clinical presentation makes it a distinct entity.

Adolescent↗
PubMed1995

Kaposi's sarcoma-associated herpesvirus-like DNA sequences in multicentric Castleman's disease.

Multicentric Castleman's disease (MCD) is an atypical lymphoproliferative disorder defined using clinical and pathologic criteria. A characteristic of the MCD is a close association with Kaposi's sarcoma (KS), which occurs during the clinical course of most human immunodeficiency virus (HIV)-associated MCD cases and also, but less frequently, in HIV-negative patients. Recently, sequences of a putative new Herpesvirus (KSHV) have been isolated and further detected in almost all the acquired immunodeficiency syndrome (AIDS) KS and in most of the non-AIDS KS samples. In this study, we searched for these Herpesvirus-like sequences in MCD samples of 31 patients. KSHV sequences were detected in 14 of 14 cases of HIV-associated MCD, including 5 cases without detectable KS. Moreover, KSHV was detected in 7 of 17 MCD cases in HIV-negative patients, including 1 case associated with a cutaneous KS. In 34 non-MCD reactive lymph nodes (follicular and/or interfollicular hyperplasia) in HIV-negative patients, KSHV was detected in only 1 case. In 1 HIV-negative case of MCD, KSHV was found in both the lymph node and peripheral blood samples. These data suggest that KSHV could play a role in the pathogenesis of MCD, especially in HIV-infected patients.

Adult↗
PubMed1995

Molecular analysis of clonality in Castleman's disease.

Castleman's disease (CD) is a rare atypical lymphoproliferative disorder that is morphologically and clinically heterogenous and is associated with a risk of developing malignant lymphoma. We report the clonality status of CD tissues in 34 patients, including 14 patients infected by the human immunodeficiency virus (HIV). Four patients presented a localized form and 30 presented a multicentric form. Two cases were associated with B-cell lymphoma, 3 cases with Hodgkin's disease, and 9 cases (8 HIV+) with Kaposi's sarcoma. Histologically, 8 cases were of the hyaline-vascular type and 26 were of the plasma cell or mixed types. The Ig and T-cell receptor (TCR) V(D)J rearrangements were analyzed using polymerase chain reaction and Southern blot. Clonal IgH rearrangements were detected in only 4 cases, ie, 2 associated with B-cell lymphoma, 1 with Hodgkin's disease, and 1 case without malignancy. A TCR gamma rearrangement of restricted junctional size was amplified in 1 HIV+ case. Finally, polyclonal VH-JH and V gamma-J gamma rearrangements were detected in the large majority of the cases, irrespective of pathologic subtypes, clinical forms, and HIV status. The lymphoid component in CD is therefore commonly reactive, and the rare occurrence of detectable monoclonal lymphoid contingents may be caused by secondary molecular events.

Adult↗
PubMed1994

Cytogenetic studies in patients with Richter's syndrome.

Cytogenetic studies in six patients with Richter's syndrome (RS) showed complex chromosome abnormalities and chromosomal instability in five. No specific chromosomal abnormality was detected. Chromosomes 14 and 11 were the most frequently involved. Neither deletion of 13q14 nor complete trisomy 12 was observed. Two patients had structural rearrangement of 12q with t(5;12)(q21-q22;q23-q24). The involvement of this region of chromosome 12 may be significant, although not specific for chronic lymphocytic leukemia. These results were compared to those found in cytogenetically studied RS patients from the literature.

Aged↗
PubMed1994

Revisited indications for bone marrow examinations in HIV-infected patients.

We reviewed the indications for and the results of bone marrow examination (BME) from HIV-infected patients as an attempt to improve its diagnostic yield. One-hundred-and-eight bone marrow specimens from 90 patients during a 3-year period were examined. A cytological, histological and microbiological study was carried out on the specimens. Forty-three evaluable examinations (40% of total) performed for cytopenia showed normo- or hypercellularity in 33 (77%). Fifty bone marrow specimens were cultured for mycobacteria with a yield of 42% when the indication was persistent fever. Positive cultures yielded Mycobacterium avium complex in 8 out of 12 patients. Twenty-seven patients had both culture and biopsy; granulomas were associated with all the positive (10/10) and with 1 out of 17 negative cultures (chi-square test: p < 0.001). A bone marrow involvement with lymphoma was found in 2 out of 6 patients with previously diagnosed lymphoma, and biopsy revealed a lymphoma in 2 patients. Morphological bone marrow examination should be associated with other techniques in order to appreciate bone marrow production. Bone marrow biopsy is useful for the investigation of persistent fever since granulomas suggestive of disseminated mycobacteria are frequent and allow a treatment to be initiated before microbiological confirmation and antibiotic susceptibility test.

Adolescent↗
PubMed1994

Alterations of the putative tumor suppressor gene p16/MTS1 in human hematological malignancies.

The chromosome band 9p21-22 is frequently rearranged or deleted in a variety of tumors including hematological malignancies. This supports the notion of a tumor suppressor gene in this chromosome region. Indeed, the p16/MTS1 gene encoding a cyclin-dependent kinase (CDK) inhibitor has been shown to be frequently deleted and/or inactivated by nonsense mutations in a number of tumors. We have examined 98 DNA samples from blood, bone marrow cells and lymph node biopsies of patients with leukemia (ALL and AML) or lymphoma (follicular lymphoma and T-cell lymphoma), using Southern blot hybridization and a p16/MTS1-specific probe. Molecular abnormalities, mainly homozygous deletions, were found principally in ALL (8 out of 22 patients), much less frequently in AML (2/32) and lymphoma (2/32). While these data argue in favor of a large involvement of p16/MTS1 in ALL, AML and lymphomas appear to be less frequently implicated.

Adult↗
PubMed1993

[Hodgkin's disease and HIV infection. Study of 40 cases].

Hodgkin's disease seems to be more frequent in HIV infected patients than in general population with peculiar clinical and pathological aspects. We describe 40 cases of Hodgkin's disease in HIV infected patients followed between 1983 and 1993.

Adult↗
PubMed1993

Production of human p53 specific monoclonal antibodies and their use in immunohistochemical studies of tumor cells.

We describe the production of 13 new monoclonal antibodies induced by the product of the human p53 tumor suppressor gene. All these monoclonal antibodies recognize human p53 irrespective of the detection technique: ELISA, immunoblot or immunoprecipitation. These antibodies can be divided into four groups according to such criteria as localization of the recognized epitopes and reactivity with p53 originating from other organisms. One monoclonal antibody was successfully used for immunohistochemistry detection of p53 accumulation in breast carcinoma. This novel panel of monoclonal antibodies represents a further tool for the study of the p53 protein.

Animals↗
PubMed1993

BCL2 gene activation and protein expression in follicular lymphoma: a report on 64 cases.

Rearrangements of the BCL2 gene and expression of bcl-2 protein were analyzed in a series of 64 cases of follicular lymphomas in order to establish a relationship between the rearrangements and the protein overexpression. Of the 64 cases, 41 showed BCL2 rearrangement involving one of the three breakpoint clusters: 30 in mbr, eight in mcr, and three in vcr. A double rearrangement mbr+vcr was detected in two cases. Twenty cases with bcl-2 protein expression in tumor cells exhibited no apparent rearrangement, suggesting the possible existence of other mechanisms activating the gene. Interestingly, expression of the LMP1 protein, the Epstein-Barr virus (EBV) encoded gene, whose capacity to induce BCL2 has been recently demonstrated, was only found in 2/41 cases in which BCL2 was rearranged. These data suggest that EBV infection is not an important mechanism in the activation of BCL2 in follicular lymphoma.

Antigens, Viral↗
PubMed1993

BCL2 complex rearrangement in follicular lymphoma: translocation mbr/JH and deletion in the vcr region of the same BCL2 allele.

Two rearrangements affecting the same allele of the BCL2 gene were characterized by molecular analysis of an untreated follicular lymphoma. The first rearrangement interested the major breakpoint region (mbr) on chromosome 18 and a JH segment on chromosome 14. The other one was located at the 5' end of the BCL2 gene, in the so called variant cluster region (vcr), and consisted of a series of deletions that removed part of a DNA region where initiation of transcription normally occurs. Interestingly, both rearrangements involved the same BCL2 allele. The simultaneous presence of mbr (or mcr) translocations and of minor rearrangements in vcr has been previously suggested by restriction map analysis in a significant number of follicular lymphomas. The significance of these abnormalities on the oncogenic process is discussed.

Alleles↗
PubMed1992

The cutaneous form of adult T-cell leukemia/lymphoma in a woman from the Ivory Coast. Clinical, immunovirologic studies and a review of the African adult T-cell leukemia/lymphoma cases.

A 36-year-old woman from Ivory Coast, who has lived in France since 1976, had multiple cutaneous nodules and tumors in 1988. Histopathologic studies showed a massive infiltration of the dermis and hypodermis by a diffuse proliferation of mature activated T-cells (CD4-positive, CD25-positive, HLA-DR-positive) with irregular nuclei. The patient did not present with a leukemic picture and only few lymphoid cells with abnormally shaped nuclei were present in the blood. Human T leukemia/lymphoma virus type I (HTLV-I) antibodies were present in the serum and specific HTLV-I pol sequences were detected in the DNA extracted from the tumor nodules and peripheral blood mononuclear cells (PBMC) using the polymerase chain reaction technique. Whereas only a polyclonal integration of HTLV-I provirus was detectable in the PBMC, a clonal integration of three HTLV-I proviruses was demonstrated in the tumor nodules DNA, establishing with certainty the diagnosis of HTLV-I-induced adult T-cell leukemia/lymphoma (ATL). This case illustrates the need for molecular studies to differentiate without ambiguity an ATL from any other type of cutaneous lymphoproliferation, even when it occurs in a HTLV-I-seropositive individual. The situation of HTLV-I-associated ATL in Africa is reviewed.

Adult↗
PubMed1992

Expression of the bcl-2 gene product in follicular lymphoma.

Expression of bcl-2 protein was analyzed in 140 cases of follicular lymphoma by immunohistologic staining of paraffin-embedded tissue; 85% of cases were positive, the frequency being related to histologic grade (100% for the small-cleaved cell type, 86% for the mixed cell type, and 76% for the large cell group). There was striking heterogeneity of bcl-2 content in a number of cases and the smaller neoplastic cells (i.e., centrocytes) were usually the most strongly labeled. In most cases, bcl-2 protein staining was much weaker in normal lymphoid cells than in the neoplastic cells. In several cases, staining for bcl-2 revealed patterns of neoplastic cell spread into adjacent tissue (e.g., normal follicles, lymphoid sinuses), and bcl-2 protein expression tended to be highest in these migratory cells.

Humans↗
PubMed1991

[Clinico-pathologic study of Kikuchi's necrotizing lymphadenitis. Report on 11 cases].

Histiocytic necrotizing lymphadenitis of Kikuchi is a rare benign disease. Characteristically, patients are young women with cervical adenopathy which may be associated with fever. Histologically, the involved lymph nodes show focal, well-circumscribed, paracortical, necrotizing lesions which contain karyorrhectic debris and aggregates of large mononuclear cells but no neutrophils. This disorder can be misdiagnosed as malignant lymphoma. The histological features seem to be related to delayed-type hypersensitivity but the antigenic stimulus is still unknown. The clinicopathological and immunohistochemical features of histiocytic necrotizing lymphadenitis in 11 patients are described. In necrotic areas, the majority of cells represent histiocytes and T cells (predominantly of CD8 phenotype). The involved lymph nodes were localized to several cervical sites (commonly jugular area).

Adolescent↗