title: Cytotoxic protein expression in non-Hodgkin's lymphomas and Hodgkin's disease.
abstract: Recent studies have shown that some peripheral T-cell lymphomas (PTCL) could be derived from lymphocytes with cytotoxic potential. Therefore, we have investigated by immunohistochemistry 34 cases of PTCL including 2 cases of hepatosplenic gamma delta PTCL and 5 cases of sinonasal NK-cell lymphomas as well as 7 cases of T-lymphoblastic lymphomas (T-LBL) for the expression of the cytotoxic proteins TIA-1 and granzyme B. In addition, 50 cases of Hodgkin's disease (HD) were investigated in order to see if these cytotoxic proteins are expressed by Hodgkin and Reed-Sternberg (HRS) cells. Expression of the TIA-1 is characteristic of cytotoxic cells regardless of their activation status whereas expression of granzymes is highly increased in activated cytotoxic cells. All the five cases of sinonasal NK-cell lymphomas expressed TIA-1 and granzyme B in most tumour cells. The two gamma delta PTCL cases expressed TIA-1 protein in most tumour cells but not granzyme B. Of the 32 other PTCL, 9 cases showed cytotoxic protein expression in tumour cells. These cases comprised 2 pleomorphic medium large cell (PML) (1 nodal and 1 intestinal) and 7 CD30 positive anaplastic large cell lymphomas (ALCL) (5 nodal and 2 cutaneous). Cytotoxic protein expression in our series appeared to be related to the location since 10/18 (55%) extranodal PTCL and NK-NHL and only 6/21 (28%) nodal PTCL expressed TIA-1, and related to histology since, in nodal PTCL, this pattern was observed in most anaplastic (5/6 cases) and in a few pleomorphic (1/9 cases) lymphomas, but not in AILD-type NHL (0/6 cases). The 7 cases of T-LBL did not express cytotoxic proteins in tumour cells. EBV was detected by EBER RNA in situ hybridization (RISH) in tumour cells in all 5 sinonasal NK-NHL and in scattered atypical cells in all 6 cases of AILD. Two of the 50 cases of HD weakly expressed TIA-1 and granzyme B in a proportion of HRS cells. EBV was detected by RISH in 19/50 cases of HD but no correlation was found between EBV status and expression of cytotoxic proteins in HRS cells. However, the finding that granzyme B positive cells were found very rarely in close vicinity of HRS cells suggests that the function of activated cytotoxic cells is locally inhibited by the HRS cells and/or the reactive cells in the vicinity of HRS cells. Taken together our data suggest that: a) sinonasal NK-cell NHL represent tumours of activated cytotoxic NK-cells, b) the hepatosplenic gamma delta PTCL represent tumours of nonactivated cytotoxic gamma delta T-cells, c) a small proportion of other PTCL, mostly anaplastic large cell lymphomas represent tumours of cytotoxic T-cells and d) only very few cases of HD expressing cytotoxic proteins in a proportion of tumour cells, could be derived from activated cytotoxic cells.
authors.affiliation: Department of Pathology, University of Crete, Greece.
authors.forename: P
authors.initials: P
authors.lastname: Kanavaros
authors.forename: M
authors.initials: M
authors.lastname: Vlychou
authors.forename: K
authors.initials: K
authors.lastname: Stefanaki
authors.forename: D
authors.initials: D
authors.lastname: Rontogianni
authors.forename: P
authors.initials: P
authors.lastname: Gaulard
authors.forename: E
authors.initials: E
authors.lastname: Pantelidaki
authors.forename: M
authors.initials: M
authors.lastname: Zois
authors.forename: K
authors.initials: K
authors.lastname: Darivianaki
authors.forename: V
authors.initials: V
authors.lastname: Georgoulias
authors.forename: M L
authors.initials: ML
authors.lastname: Boulland
authors.forename: V
authors.initials: V
authors.lastname: Gorgoulis
authors.forename: C
authors.initials: C
authors.lastname: Kittas
mesh_terms: D053804:Granzymes; D006689:Hodgkin Disease / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007694:Killer Cells, Natural / Q000276:immunology; D008198:Lymph Nodes / Q000737:chemistry; D008213:Lymphocyte Activation; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology* / Q000378:metabolism; D008565:Membrane Proteins / Q000032:analysis*; D039102:Poly(A)-Binding Proteins; D011506:Proteins; D016601:RNA-Binding Proteins / Q000032:analysis*; D012697:Serine Endopeptidases / Q000032:analysis*; D000074019:T-Cell Intracellular Antigen-1; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D008565:Membrane Proteins; D039102:Poly(A)-Binding Proteins; D011506:Proteins; D016601:RNA-Binding Proteins; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases