scholarly journals High incidence of the t(2;5)(p23;q35) translocation in anaplastic large cell lymphoma and its lack of detection in Hodgkin's disease. Comparison of cytogenetic analysis, reverse transcriptase-polymerase chain reaction, and P-80 immunostaining

Blood ◽  
1996 ◽  
Vol 87 (1) ◽  
pp. 284-291 ◽  
Author(s):  
L Lamant ◽  
F Meggetto ◽  
T al Saati ◽  
L Brugieres ◽  
BB de Paillerets ◽  
...  
Keyword(s):  
Hodgkin's Disease ◽  
Cytogenetic Analysis ◽  
Cell Lymphoma ◽  
Hodgkin’S Disease ◽  
Large Cell ◽  
Rt Pcr ◽  
Chain Reaction ◽  
Polymerase Chain ◽  
Large Cell Lymphoma ◽  
Alk Protein

Abstract Fifty-six cases of anaplastic large cell lymphoma (ALCL), 23 cases of Hodgkin's disease, and 16 cases of diffuse large cell lymphoma were investigated for the t(2;5)(p23;q35) translocation. The translocation was detected by using cytogenetic analysis, reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry with P80 antibody directed against the kinase domain of anaplastic lymphoma kinase (ALK) of the chimeric NPM/ALK protein. In all but three cases of ALCL, we found an agreement between cytogenetic analysis, RT-PCR, and P80 staining. However, in one case, the t(2;5) translocation was detected with cytogenetic analysis, but RT-PCR and P80 staining were found to be negative. Conversely, in another case the karyotype was normal, but the hybrid mRNA and P80 staining were found to be positive. In one case, malignant cells showed a translocation involving chromosomes 1q25 and 2p23 and were strongly positive for P80 staining. Such a result could be expected because P80 antibody detects the kinase domaine of the ALK protein encoded by chromosome 2p23. Overall 73.2% (41 of 56) of cases were found to be positive. However, the highest percentage (23 of 26 cases; 88.5%) of P80 positive cases was found in children compared with 60% (18 of 30 cases) in adult ALCL (P < .05). In Hodgkin's disease, Reed-Sternberg cells were found to be clearly negative by RT-PCR and with P80 antibody. The latter results suggest that Hodgkin's disease and t(2;5)-positive ALCL are distinct biological entities and that the demonstration of the t(2;5) translocation is of diagnostic importance in differentiating these two entities. The results of the present study indicate that immunohistochemistry with P80 antibody is a reliable method for detecting NPM/ALK chimeric protein.

scholarly journals High incidence of the t(2;5)(p23;q35) translocation in anaplastic large cell lymphoma and its lack of detection in Hodgkin's disease. Comparison of cytogenetic analysis, reverse transcriptase-polymerase chain reaction, and P-80 immunostaining

Blood ◽  
1996 ◽  
Vol 87 (1) ◽  
pp. 284-291 ◽  
Author(s):  
L Lamant ◽  
F Meggetto ◽  
T al Saati ◽  
L Brugieres ◽  
BB de Paillerets ◽  
...  
Keyword(s):  
Hodgkin's Disease ◽  
Cytogenetic Analysis ◽  
Cell Lymphoma ◽  
Hodgkin’S Disease ◽  
Large Cell ◽  
Rt Pcr ◽  
Chain Reaction ◽  
Polymerase Chain ◽  
Large Cell Lymphoma ◽  
Alk Protein

Fifty-six cases of anaplastic large cell lymphoma (ALCL), 23 cases of Hodgkin's disease, and 16 cases of diffuse large cell lymphoma were investigated for the t(2;5)(p23;q35) translocation. The translocation was detected by using cytogenetic analysis, reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry with P80 antibody directed against the kinase domain of anaplastic lymphoma kinase (ALK) of the chimeric NPM/ALK protein. In all but three cases of ALCL, we found an agreement between cytogenetic analysis, RT-PCR, and P80 staining. However, in one case, the t(2;5) translocation was detected with cytogenetic analysis, but RT-PCR and P80 staining were found to be negative. Conversely, in another case the karyotype was normal, but the hybrid mRNA and P80 staining were found to be positive. In one case, malignant cells showed a translocation involving chromosomes 1q25 and 2p23 and were strongly positive for P80 staining. Such a result could be expected because P80 antibody detects the kinase domaine of the ALK protein encoded by chromosome 2p23. Overall 73.2% (41 of 56) of cases were found to be positive. However, the highest percentage (23 of 26 cases; 88.5%) of P80 positive cases was found in children compared with 60% (18 of 30 cases) in adult ALCL (P < .05). In Hodgkin's disease, Reed-Sternberg cells were found to be clearly negative by RT-PCR and with P80 antibody. The latter results suggest that Hodgkin's disease and t(2;5)-positive ALCL are distinct biological entities and that the demonstration of the t(2;5) translocation is of diagnostic importance in differentiating these two entities. The results of the present study indicate that immunohistochemistry with P80 antibody is a reliable method for detecting NPM/ALK chimeric protein.

scholarly journals Transcripts of the npm-alk fusion gene in anaplastic large cell lymphoma, Hodgkin's disease, and reactive lymphoid lesions

Blood ◽  
1995 ◽  
Vol 86 (9) ◽  
pp. 3517-3521 ◽  
Author(s):  
PG Elmberger ◽  
MD Lozano ◽  
DD Weisenburger ◽  
W Sanger ◽  
WC Chan
Keyword(s):  
Anaplastic Large Cell Lymphoma ◽  
Hodgkin's Disease ◽  
Fusion Gene ◽  
Cell Lymphoma ◽  
Cytogenetic Study ◽  
Hodgkin’S Disease ◽  
Large Cell ◽  
Rt Pcr ◽  
Anaplastic Lymphoma ◽  
Large Cell Lymphoma

Anaplastic large cell lymphoma (ALCL) and Hodgkin's disease (HD) have some pathologic and immunohistochemical similarities, and a histogenetic relationship between them has been suggested by some investigators. By cytogenetic study, the t(2;5)(p23;q35) translocation appears to be unique for ALCL. The breakpoints of the t(2;5)(p23;q35) have recently been cloned and are reported to involve a novel tyrosine kinase gene, anaplastic lymphoma kinase (alk), on chromosome 2 and the nucleophosmin gene (npm) on chromosome 5. Therefore, we studied the frequency of npm-alk translocation in ALCL using a reverse transcriptase-polymerase chain reaction (RT-PCR) assay. We also studied HD and a variety of reactive lymphoid lesions since there is contradictory information in the literature on the occurrence of the npm-alk rearrangement in HD. We detected npm-alk hybrid mRNA in 8 of 22 cases of ALCL (36%), but none of the 21 cases of HD or the 11 cases with reactive lesions contained amplifiable template. All positive ALCL had the T or indeterminate phenotype and occurred in young adults or children. There was very good correlation between a cytogenetically detectable t(2;5) and a positive signal by RT-PCR. Our results indicate a selective but relatively infrequent association between the t(2;5) and ALCL of T or indeterminate phenotype, not shared with HD or reactive hyperplasia.

scholarly journals Molecular characterization of the t(2;5) (p23; q35) translocation in anaplastic large cell lymphoma (Ki-1) and Hodgkin's disease

Blood ◽  
1996 ◽  
Vol 87 (3) ◽  
pp. 1081-1088 ◽  
Author(s):  
HT Yee ◽  
M Ponzoni ◽  
A Merson ◽  
M Goldstein ◽  
A Scarpa ◽  
...  
Keyword(s):  
Southern Blot ◽  
Anaplastic Large Cell Lymphoma ◽  
Blot Analysis ◽  
Hodgkin's Disease ◽  
Southern Blot Analysis ◽  
Cell Lymphoma ◽  
Hodgkin’S Disease ◽  
Large Cell ◽  
Rt Pcr ◽  
Large Cell Lymphoma

The precise cellular origin and the pathogenetic mechanism(s) leading to the neoplastic transformation of anaplastic large cell lymphoma (ALCL) and the Reed-Sternberg cell of Hodgkin's disease (HD) remains largely uncertain. Classical cytogenetic analysis has shown a unique translocation involving bands 2p23 and 5q35 bands in a variable number of ALCLs. It has been recently shown that the nucleophosmin/B23 (NPM) gene (5q35) and a novel anaplastic lymphoma kinase (ALK; 2p23) are the fused genes of t(2;5). To investigate the presence and the precise frequency of NPM-ALK gene products among ALCL and HD cases, a large and well-characterized panel of ALCL (n = 49) and HD (n = 72) cases was studied using multiple strategies including reverse transcriptase- polymerase chain reaction (RT-PCR), Southern blot analysis, and immunohistochemistry. Overall, 6 (3 T and 3 null) of 49 ALCL and 3 (2 nodular sclerosis and 1 mixed cellularity) of 72 HD showed the presence of NPM-ALK transcripts by RT-PCR. NPM-ALK gene rearrangements were detected in all RT-PCR, NPM-ALK-positive ALCL by Southern blot analysis. Furthermore, in all the available cases we were able to show the presence of ALK-related protein using a specific polyclonal antiserum recognizing the cytoplasmic domain of ALK by immunohistochemistry. Our data show that NPM-ALK gene transcripts are identified in a subpopulation of ALCL, almost exclusively in T or null cell in origin, and in rare cases of HD. These findings show that some HD may be closely related to ALCL, giving us new insights on the pathogenesis and possibly biologic evolution of HD.

scholarly journals Nodular lymphocyte-predominant Hodgkin's disease associated with large- cell lymphoma: analysis of Ig gene rearrangements by V-J polymerase chain reaction

Blood ◽  
1996 ◽  
Vol 88 (2) ◽  
pp. 657-666 ◽  
Author(s):  
TC Greiner ◽  
RD Gascoyne ◽  
ME Anderson ◽  
DW Kingma ◽  
SA Adomat ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
B Cell ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Large Cell ◽  
Single Step ◽  
Chain Gene ◽  
Gene Rearrangements ◽  
Chain Reaction ◽  
Polymerase Chain

The clonality of nodular lymphocyte-predominant Hodgkin's disease (NLPHD) and the relationship to composite or sequential large-cell lymphomas (LCLs) is poorly understood. Clonal Ig heavy-chain gene rearrangements (lgHGR) have infrequently been observed in NLPHD by Southern hybridization. The goals of this study were (1) to determine if IgHGR could be identified by polymerase chain reaction (PCR) techniques in the LCL associated with NLPHD; (2) to determine if the lgHGR identified in the LCL could also be found in the associated NLPHD; and (3) to determine if Epstein-Barr virus (EBV) played a role a role in histologic progression to LCL. Using consensus primers to conserved regions in the lgH variable (V) and joining (J) region genes, we analyzed formalin-fixed paraffin-embedded sections from the biopsies of 25 patients referred to the National Cancer Institute (NCI) registry for NLPHD and LCL using both single-step and seminested V-J PCR. The histologically aggressive component was further subclassified as frank LCL or as L&H-cell-rich, but not fulfilling criteria for LCL. Matched samples representing both NLPHD and aggressive components were available in 13 cases. In 12 cases, only one component was available (aggressive, n = 8; NLPHD, n = 4). In addition, we also amplified, with 32P labeling, 12 cases of NLPHD without associated LCL. Two clonal IgHGR were identified in 29 cases (7%) of typical NLPHD, both of which were associated with LCL containing a similar sized band by PCR. The clonal identity of the bands in the NLPHD and associated LCL was confirmed by sequencing the products in these two cases. Eight of 10 cases (80%) of LCL associated with NLPHD contained a clonal band by this technique. By contrast, none of the cases classified as L&H-cell- rich contained an IgHGR. The single-step and seminested PCR methods produced identical results. All clonal LCLs were studied for EBV sequences by in situ hybridization using the EBER1 probe, and were negative. We conclude that the LCLs associated with NLPHD are clonal B- cell malignancies. However, by these methods, the same clone can be identified in only a minority of cases of NLPHD and LCL. EBV does not appear to play a role in histologic progression. Moreover, our results suggest that many cases suspected of being LCL may actually represent NLPHD with increased numbers of L&H cells. In histologically equivocal cases, the diagnosis of LCL should be reserved for those cases in which a clonal B-cell neoplasm can be demonstrated.

scholarly journals Absence of the t(2;5) in Hodgkin's disease [see comments]

Blood ◽  
1995 ◽  
Vol 85 (10) ◽  
pp. 2845-2847 ◽  
Author(s):  
LM Weiss ◽  
JR Lopategui ◽  
LH Sun ◽  
OW Kamel ◽  
CH Koo ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Blot Hybridization ◽  
Southern Blot Hybridization ◽  
Large Cell ◽  
Common Finding ◽  
Chain Reaction ◽  
Polymerase Chain ◽  
Hodgkin's Lymphomas

The cytogenetics of Hodgkin's disease (HD) is poorly understood. However, a t(2;5) is a common finding in CD30+ anaplastic large cell lymphoma (ALCL), a neoplasm thought by some to be closely related to HD. Recently, the t(2;5) has been cloned and found to represent fusion of the NPM gene with the ALK gene. Using Southern blot hybridization, one group has reported finding rearrangements of NPM in a proportion of cases of both ALCL and HD. In the current study, we used a highly sensitive reverse transcriptase-polymerase chain reaction methodology to analyze 34 cases of HD for the t(2;5). We were unable to find polymerase chain reaction evidence for the t(2;5) in any of the cases of HD, a result significantly different from our previous study of CD30+ non-Hodgkin's lymphomas (P < .02) including ALCL (P < .04), using identical methods. Our results do not support the hypothesis that the t(2;5) represents a common chromosomal abnormality for both HD and ALCL.

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