Immunogenotypic and Viral Analyzes of Lethal Midline Granuloma
| Project/Area Number |
04671046
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Otorhinolaryngology
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| Research Institution | WAKAYAMA MEDICAL COLLEGE (1993-1994)
Sapporo Medical University (1992) |
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Principal Investigator |
YAMANAKA Noboru Wakayama Medical College, Department of Otolaryngology, Professor, 耳鼻咽喉科, 教授 (10136963)
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| Co-Investigator(Kenkyū-buntansha) |
山中 昇 和歌山県立医科大学, 耳鼻咽喉科, 教授 (10136963)
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| Project Period (FY) |
1992 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1994: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1993: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1992: ¥900,000 (Direct Cost: ¥900,000)
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| Keywords | lethal midline granuloma / T cell receptor / genotypic analysis / Southern blot analysis / Epstern-Barr virus |
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| Research Abstract |
So-called lethal midline granuloma is of great clinical and theoretical interest. The etiology of lethal midline granuloma is unknown and the pathogenesis is variable, with debate as to precise classification and natural history. In this study, we reported immunopathological, immunogenotypic and viral features in 11 cases of lethal midline granuloma. The histopathological diagnosis of their biopsy specimens was initially polymorphic reticulosis or midline malignant reticulosis. Immunohistologic study of the specimens revealed that immature or atypical cells had phenotypes of T-cells, CD2, CD3, CD4, CD8 in 9 cases and of natural killer cells, CD2 and CD56 in other 2 cases. Those cells were also found to be positive for HLA-DR,which indicated that they were activated cells. Immunohistology in T-cells, however, was not able to give a similar clue to clonarity as it was possible within B-cells neoplasms by immunophenotyping the light chains. With the establishment of cDNA probes for the T-
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cell receptor genes it was possible to analyze neoplasms of lymphocyte origin for lineage and clonality. The Southern blot analysis of 7 cases showed rearrangement of TCR gene, TCRbeta or TCRgamma chain in 5 cases, whereas none of them showed rearragement of immunoglobulin heavy chain. These findings represented conclusive evidence for a monoclonal T-cell proliferation within the majority of lethal midline granuloma. In addition, phenotypic and immunogenotypic analyzes revealed that some of the disease originated in natural killer cell lineage. EpsteinBarr virus (EBV) DNA was detected in the nasal tumour biopsy specimens by Southern blotting and in vitro hybridisation with simultaneous detection of EBV determined nuclear antigen (EBNA) and T cell surface markers by two color immunofluorescence. Further immuno-fluorescence and northern blotting revealed that EBNA2 gene and also latent membrane protein gene were expressed in the nasal tumour cells. The patients had high titres of antibodies to EBV.These findings suggest that lethal midline granuloma is causally associated with EBV.
On the ground of immungenotypi and viral studies, lethal midline granuloma histologically diagnosed as polymorphic reticulosis/midline malignant reticulosis are proven to be a Epstein-Barr virus associated T-cell lymphoproliferative disorder. Less
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Report
(4 results)
Research Products
(15 results)
