Primary mediastinal B-cell lymphoma: Detection of BCL2 gene rearrangements by PCR analysis and FISH

Cherie H. Dunphy, Dennis P. O'Malley, Liang Cheng, Tina Y. Fodrie, Sherrie L. Perkins, Kathleen Kaiser-Rogers

Research output: Contribution to journalArticle

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Abstract

Primary mediastinal large B-cell lymphoma (PMBCL) has a characteristic clinical presentation, morphology, and immunophenotype, representing a clinically favorable subgroup of diffuse large B-cell lymphoma (DLBCL). By gene expression profiling (GEP), PMBCL shares features with classical Hodgkin lymphoma (cHL). Of further interest, BCL6 gene mutations and BCL6 and/or MUM1 expression in a number of PMBCLs have supported an activated B-cell (ABC) origin. Several studies, including GEP, have failed to detect BCL2 gene rearrangements (GRs) in PMBCL. An index case of t(14; 18)+ PMBCL prompted our study of the incidence of BCL2 GRs in PMBCL by polymerase chain reaction (PCR)/fluorescence in situ hybridization (FISH) analyses and its possible clinical impact. Twenty-five retrospectively identified, well-defined PMBCLs (five with cytogenetics) from three institutions were analyzed for a BCL2 GR by PCR/FISH analyses. The formalin-fixed, paraffin-embedded tissue blocks of 24 available cases were also analyzed by BCL2 immunohistochemistry (IHC). Of the five with cytogenetics, two had a t(14; 18) (q32; q21). Of the 25 analyzed by PCR, 2 had no amplifiable DNA (aDNA), including 1 t(14; 18)+ case. Of those with aDNA, two showed a BCL2 GR; by FISH analysis, three demonstrated a BCL2 GR. BCL2 protein expression by IHC analysis was variably detected in 21 out of 24 (strongly, uniformly expressed: 6, including all with a t(14; 18) or a BCL2 gene rearrangement; moderately weakly expressed in a subset of the malignant cells: 15). Available clinical follow-up of this BCL2+ subset showed a similar course to the other PMBCL cases. Our results imply that a subset of PMBCL [(4 out of 24 analyzed) in our series] may be of GC origin. A larger study is necessary to determine any clinical significance.

Original languageEnglish
Pages (from-to)77-84
Number of pages8
JournalJournal of Hematopathology
Volume1
Issue number2
DOIs
StatePublished - 2008

Fingerprint

Gene Rearrangement
B-Cell Lymphoma
Fluorescence In Situ Hybridization
Polymerase Chain Reaction
Gene Expression Profiling
Cytogenetics
Proto-Oncogene Proteins c-bcl-2
Immunohistochemistry
Lymphoma, Large B-Cell, Diffuse
DNA
Hodgkin Disease
Paraffin
Formaldehyde
B-Lymphocytes
Cohort Studies
Mutation
Genes

Keywords

  • BCL2 gene
  • PCR and FISH analysis
  • Primary mediastinal B-cell lymphoma

ASJC Scopus subject areas

  • Hematology
  • Pathology and Forensic Medicine
  • Histology

Cite this

Primary mediastinal B-cell lymphoma : Detection of BCL2 gene rearrangements by PCR analysis and FISH. / Dunphy, Cherie H.; O'Malley, Dennis P.; Cheng, Liang; Fodrie, Tina Y.; Perkins, Sherrie L.; Kaiser-Rogers, Kathleen.

In: Journal of Hematopathology, Vol. 1, No. 2, 2008, p. 77-84.

Research output: Contribution to journalArticle

Dunphy, Cherie H. ; O'Malley, Dennis P. ; Cheng, Liang ; Fodrie, Tina Y. ; Perkins, Sherrie L. ; Kaiser-Rogers, Kathleen. / Primary mediastinal B-cell lymphoma : Detection of BCL2 gene rearrangements by PCR analysis and FISH. In: Journal of Hematopathology. 2008 ; Vol. 1, No. 2. pp. 77-84.
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AB - Primary mediastinal large B-cell lymphoma (PMBCL) has a characteristic clinical presentation, morphology, and immunophenotype, representing a clinically favorable subgroup of diffuse large B-cell lymphoma (DLBCL). By gene expression profiling (GEP), PMBCL shares features with classical Hodgkin lymphoma (cHL). Of further interest, BCL6 gene mutations and BCL6 and/or MUM1 expression in a number of PMBCLs have supported an activated B-cell (ABC) origin. Several studies, including GEP, have failed to detect BCL2 gene rearrangements (GRs) in PMBCL. An index case of t(14; 18)+ PMBCL prompted our study of the incidence of BCL2 GRs in PMBCL by polymerase chain reaction (PCR)/fluorescence in situ hybridization (FISH) analyses and its possible clinical impact. Twenty-five retrospectively identified, well-defined PMBCLs (five with cytogenetics) from three institutions were analyzed for a BCL2 GR by PCR/FISH analyses. The formalin-fixed, paraffin-embedded tissue blocks of 24 available cases were also analyzed by BCL2 immunohistochemistry (IHC). Of the five with cytogenetics, two had a t(14; 18) (q32; q21). Of the 25 analyzed by PCR, 2 had no amplifiable DNA (aDNA), including 1 t(14; 18)+ case. Of those with aDNA, two showed a BCL2 GR; by FISH analysis, three demonstrated a BCL2 GR. BCL2 protein expression by IHC analysis was variably detected in 21 out of 24 (strongly, uniformly expressed: 6, including all with a t(14; 18) or a BCL2 gene rearrangement; moderately weakly expressed in a subset of the malignant cells: 15). Available clinical follow-up of this BCL2+ subset showed a similar course to the other PMBCL cases. Our results imply that a subset of PMBCL [(4 out of 24 analyzed) in our series] may be of GC origin. A larger study is necessary to determine any clinical significance.

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