Anaplastic large-cell lymphomas of T-cell and null-cell phenotype express cytotoxic molecules.
To further specify the cellular origin and nature of anaplastic large-cell lymphoma (ALCL) and its relationship to other lymphoid neoplasms, particularly Hodgkin's disease (HD), we investigated the presence of cytotoxic molecules in a large well-characterized series of these tumors. For expression of the cytotoxic molecules perforin and granzyme B, in situ hybridization (ISH) and immunohistology were used, respectively. Overall, 23 of 25 ALCLs of T/null phenotype and five (three mixed cellularity and two nodular sclerosis) of 57 HD cases showed the presence of perforin transcripts and/or granzyme B molecules in neoplastic cells. Polymerase chain reaction (PCR) analysis of ALCLs showed that most (10 of 11) cases of null-cell ALCL (null-ALCL) contained a clonal rearrangement of T-cell receptor beta-chain genes, as did T-cell ALCL (T-ALCL; 9 of 10 cases). However, both cytotoxic molecules and clonally rearranged T-cell receptor beta-chain genes were absent in seven of seven and eight of nine cases of B-cell ALCL (B-ALCL), respectively. These data show that all or nearly all T-ALCLs, irrespective of the clinical subform or the lack of T-cell-associated molecules, are derived from activated cytotoxic T cells. The same appears to be true for the neoplastic cells of rare HD cases. These findings indicate that T-ALCLs are different from B-ALCLs and the majority of HD cases, and suggest that some HD cases, especially those with T-cell antigen-positive tumor cells, may be closely related to T-ALCL, at least in terms of cellular origin.
Foss
H D
HD
Institute of Pathology, Klinikum Benjamin Franklin, Free University of Berlin, Germany.
Anagnostopoulos
I
I
Araujo
I
I
Assaf
C
C
Demel
G
G
Kummer
J A
JA
Hummel
M
M
Stein
H
H
D015415:Biomarkers; D002454:Cell Differentiation; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D053804:Granzymes; D006689:Hodgkin Disease / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation; D008215:Lymphocytes, Null / Q000378:metabolism* / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000378:metabolism / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism* / Q000473:pathology; D016399:Lymphoma, T-Cell / Q000378:metabolism* / Q000473:pathology; D016411:Lymphoma, T-Cell, Peripheral / Q000378:metabolism / Q000473:pathology; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D016539:Reed-Sternberg Cells / Q000378:metabolism / Q000473:pathology; D012697:Serine Endopeptidases / Q000096:biosynthesis*; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism* / Q000473:pathology
D015415:Biomarkers; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases