title: Expression of cytotoxic molecules in intestinal T-cell lymphomas. The German Study Group on Intestinal Non-Hodgkin Lymphoma.
abstract: Intestinal T-cell lymphoma (ITCL) represents a subgroup of peripheral T-cell lymphomas which is thought to arise from alpha beta intraepithelial T-lymphocytes. Since these lymphocytes may contain cytotoxic molecules, the question of whether this also holds true for ITCL arises. Twenty ITCL cases were examined for the presence of granzyme B, perforin, and T-cell-restricted intracellular antigen (TIA-1)/granule membrane protein of 17 kD (GMP-17). Two molecules with restricted expression in cytotoxic cells, granzyme B and perforin, were detected by immunocytochemistry and by in situ hybridization with an isotopically labelled RNA probe, respectively. Immunocytochemistry was also performed with the antibody 2G9, which recognizes two molecules, one expressed by cytotoxic cells (TIA-1) and the other found in granulocytes and cytotoxic cells (GMP-17). Granzyme B, TIA-1/GMP-17, and perforin were found in the neoplastic cells of 16/19 cases, 19/20 cases, and 16/17 cases, respectively, of ITCL, but not in the tumour cells of the control group, which consisted of intestinal B-cell lymphomas (five cases) and CD8-negative peripheral nodal T-cell lymphomas (six cases). At least one of these molecules was expressed in the tumour cells of all ITCL cases. 2G9 proved to be the most sensitive immunohistological marker, since reactivity with this antibody was not only observed in the highest number of cases, but also found in high numbers of neoplastic cells in positive cases. In conclusion, ITCL appears to show cytotoxic differentiation in all cases. In conjunction with immunophenotypic and genotypic data, our results support a uniform derivation of this tumour from intraepithelial alpha beta cytotoxic T-lymphocytes.
authors.affiliation: Department of Gastroenterology, Klinikum Benjamin Franklin, Free University of Berlin, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Daum
authors.forename: H D
authors.initials: HD
authors.lastname: Foss
authors.forename: I
authors.initials: I
authors.lastname: Anagnostopoulos
authors.forename: B
authors.initials: B
authors.lastname: Dederke
authors.forename: G
authors.initials: G
authors.lastname: Demel
authors.forename: I
authors.initials: I
authors.lastname: Araujo
authors.forename: E O
authors.initials: EO
authors.lastname: Riecken
authors.forename: H
authors.initials: H
authors.lastname: Stein
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002446:Celiac Disease / Q000150:complications; D005260:Female; D015870:Gene Expression; D053804:Granzymes; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007414:Intestinal Neoplasms / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D016399:Lymphoma, T-Cell / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D008875:Middle Aged; D054353:Perforin; D039102:Poly(A)-Binding Proteins; D052899:Pore Forming Cytotoxic Proteins; D011506:Proteins; D016601:RNA-Binding Proteins; D012697:Serine Endopeptidases; D000074019:T-Cell Intracellular Antigen-1
chemical_list: D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C499363:NKG7 protein, human; D039102:Poly(A)-Binding Proteins; D052899:Pore Forming Cytotoxic Proteins; D011506:Proteins; D016601:RNA-Binding Proteins; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human; D054353:Perforin; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases