Skip to main content

01.11.2014 | Research Article

Evaluation diagnostic usefulness of immunoglobulin light chains (Igκ, Igλ) and incomplete IGH D-J clonal gene rearrangements in patients with B-cell non-Hodgkin lymphomas using BIOMED-2 protocol

Erschienen in: Clinical and Translational Oncology | Ausgabe 11/2014

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Evaluation diagnostic usefulness of immunoglobulin light chains (Igκ, Igλ) and incomplete IGH D-J clonal gene rearrangements in formalin-fixed, paraffin-embedded (FFPE) tissue of patients with B-cell non-Hodgkin lymphomas (B-NHL).

Materials and methods

This study was performed on samples from 70 patients with B-NHL, including two cases of follicular lymphoma (FL), 20 cases of diffuse large B-cell lymphoma (DLBCL), one case of mantle cell lymphoma (MCL), and 47 cases of B-cell neoplasm (non-classified), which had been previously assessed for complete IGH clonality, and failure to clarify gene rearrangements. We used a gold standard multiplex PCR protocol provided by European Biomedicine and Health (BIOMED-2) Concerted Action Project BMH4-CT98-3936 for improvement of diagnosis and analysis of clonality gene rearrangement in lymphoma malignancies.

Results

Our results revealed a total positive monoclonality of 89 % (62/70) in Igκ, Igλ, and 11.4 % (8/70) polyclonality in gene rearrangements assay. The samples with positive clonality consisting (Igκ: 45 %, Igλ: 55 %) in DLBCL, (Igκ: 100 %) in FL, (Igλ: 100 %) in MCL, and (Igκ: 47 %, Igλ: 36 %) in B-cell neoplasm non-classified. None of the incomplete IGH DJ immunoglobulin gene families (0 %) showed monoclonality, and all samples demonstrated polyclonality pattern.

Conclusions

Our findings on FFPE tissue revealed that immunoglobulin light chains clonality gene rearrangements assays using BIOMED-2 protocol, could be considered a valuable and reliable method for clonality detection, particularly in cases of failure of complete IGH gene rearrangements analysis. Clonal Ig gene rearrangements assay is applicable for routine diagnostic testing of lymphoproliferative disorders and as a reliable method for differentiating between malignant and benign lymphoma disorders.
Literatur
1.
Zurück zum Zitat World Health Organization. WHO Classification of tumours of haematopoietic and lymphoid tissues. Lyon: International Agency for Research on Cancer; 2008. World Health Organization. WHO Classification of tumours of haematopoietic and lymphoid tissues. Lyon: International Agency for Research on Cancer; 2008.
2.
Zurück zum Zitat Schuetz JM, Daley D, Leach S, Conde L, Berry BR, Gallagher RP, et al. Non-Hodgkin lymphoma risk and variants in genes controlling lymphocyte development. PLoS ONE. 2013;8:e75170.PubMedCrossRefPubMedCentral Schuetz JM, Daley D, Leach S, Conde L, Berry BR, Gallagher RP, et al. Non-Hodgkin lymphoma risk and variants in genes controlling lymphocyte development. PLoS ONE. 2013;8:e75170.PubMedCrossRefPubMedCentral
3.
Zurück zum Zitat Visser OJ, Perk LR, Zijlstra JM, van Dongen GA, Huijgens PC, van de Loosdrecht AA. Radioimmunotherapy for indolent B-cell non-Hodgkin lymphoma in relapsed, refractory and transformed disease. BioDrugs. 2006;20:201–7.PubMedCrossRef Visser OJ, Perk LR, Zijlstra JM, van Dongen GA, Huijgens PC, van de Loosdrecht AA. Radioimmunotherapy for indolent B-cell non-Hodgkin lymphoma in relapsed, refractory and transformed disease. BioDrugs. 2006;20:201–7.PubMedCrossRef
4.
Zurück zum Zitat Alt FW, Oltz EM, Young F, Gorman J, Taccioli G, Chen J. VDJ recombination. Immunol Today. 1992;13:306–14.PubMedCrossRef Alt FW, Oltz EM, Young F, Gorman J, Taccioli G, Chen J. VDJ recombination. Immunol Today. 1992;13:306–14.PubMedCrossRef
5.
Zurück zum Zitat González D, van der Burg M, García-Sanz R, Fenton JA, Langerak AW, González M, et al. Immunoglobulin gene rearrangements and the pathogenesis of multiple myeloma. Blood. 2007;110:3112–21.PubMedCrossRef González D, van der Burg M, García-Sanz R, Fenton JA, Langerak AW, González M, et al. Immunoglobulin gene rearrangements and the pathogenesis of multiple myeloma. Blood. 2007;110:3112–21.PubMedCrossRef
6.
Zurück zum Zitat Gawad C, Pepin F, Carlton VE, Klinger M, Logan AC, Miklos DB, et al. Massive evolution of the immunoglobulin heavy chain locus in children with B precursor acute lymphoblastic leukemia. Blood. 2012;120:4407–17.PubMedCrossRefPubMedCentral Gawad C, Pepin F, Carlton VE, Klinger M, Logan AC, Miklos DB, et al. Massive evolution of the immunoglobulin heavy chain locus in children with B precursor acute lymphoblastic leukemia. Blood. 2012;120:4407–17.PubMedCrossRefPubMedCentral
7.
Zurück zum Zitat Küppers R, Zhao M, Hansmann M, Rajewsky K. Tracing B-cell development in human germinal centres by molecular analysis of single cells picked from histological sections. EMBO J. 1993;12:4955.PubMedPubMedCentral Küppers R, Zhao M, Hansmann M, Rajewsky K. Tracing B-cell development in human germinal centres by molecular analysis of single cells picked from histological sections. EMBO J. 1993;12:4955.PubMedPubMedCentral
8.
Zurück zum Zitat Li A-H, Rosenquist R, Forestier E, Lindh J, Roos G. Detailed clonality analysis of relapsing precursor B acute lymphoblastic leukemia: implications for minimal residual disease detection. Leuk Res. 2001;25:1033–45.PubMedCrossRef Li A-H, Rosenquist R, Forestier E, Lindh J, Roos G. Detailed clonality analysis of relapsing precursor B acute lymphoblastic leukemia: implications for minimal residual disease detection. Leuk Res. 2001;25:1033–45.PubMedCrossRef
9.
Zurück zum Zitat Szczepański T, Willemse MJ, Brinkhof B, van Wering ER, van der Burg M, van Dongen JJ. Comparative analysis of Ig and TCR gene rearrangements at diagnosis and at relapse of childhood precursor-B–ALL provides improved strategies for selection of stable PCR targets for monitoring of minimal residual disease. Blood. 2002;99:2315–23.PubMedCrossRef Szczepański T, Willemse MJ, Brinkhof B, van Wering ER, van der Burg M, van Dongen JJ. Comparative analysis of Ig and TCR gene rearrangements at diagnosis and at relapse of childhood precursor-B–ALL provides improved strategies for selection of stable PCR targets for monitoring of minimal residual disease. Blood. 2002;99:2315–23.PubMedCrossRef
10.
Zurück zum Zitat He J, Wu J, Jiao Y, Wagner-Johnston N, Ambinder RF, Diaz LA Jr, et al. IgH gene rearrangements as plasma biomarkers in non-Hodgkin’s lymphoma patients. Oncotarget. 2011;2:178.PubMedPubMedCentral He J, Wu J, Jiao Y, Wagner-Johnston N, Ambinder RF, Diaz LA Jr, et al. IgH gene rearrangements as plasma biomarkers in non-Hodgkin’s lymphoma patients. Oncotarget. 2011;2:178.PubMedPubMedCentral
11.
Zurück zum Zitat Van Dongen J, Langerak A, Brüggemann M, Evans P, Hummel M, Lavender F, et al. Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia. 2003;17:2257–317.PubMedCrossRef Van Dongen J, Langerak A, Brüggemann M, Evans P, Hummel M, Lavender F, et al. Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia. 2003;17:2257–317.PubMedCrossRef
12.
Zurück zum Zitat Evans P, Pott C, Groenen P, Salles G, Davi F, Berger F, et al. Significantly improved PCR-based clonality testing in B-cell malignancies by use of multiple immunoglobulin gene targets. Report of the BIOMED-2 Concerted Action BHM4-CT98-3936. Leukemia. 2006;21:207–14.PubMedCrossRef Evans P, Pott C, Groenen P, Salles G, Davi F, Berger F, et al. Significantly improved PCR-based clonality testing in B-cell malignancies by use of multiple immunoglobulin gene targets. Report of the BIOMED-2 Concerted Action BHM4-CT98-3936. Leukemia. 2006;21:207–14.PubMedCrossRef
13.
Zurück zum Zitat Langerak AW, van Dongen JJ. Multiple clonal Ig/TCR products: implications for interpretation of clonality findings. J Hematopathology. 2012;5:35–43.CrossRef Langerak AW, van Dongen JJ. Multiple clonal Ig/TCR products: implications for interpretation of clonality findings. J Hematopathology. 2012;5:35–43.CrossRef
14.
Zurück zum Zitat Isola J, DeVries S, Chu L, Ghazvini S, Waldman F. Analysis of changes in DNA sequence copy number by comparative genomic hybridization in archival paraffin-embedded tumor samples. Am J Pathol. 1994;145:1301.PubMedPubMedCentral Isola J, DeVries S, Chu L, Ghazvini S, Waldman F. Analysis of changes in DNA sequence copy number by comparative genomic hybridization in archival paraffin-embedded tumor samples. Am J Pathol. 1994;145:1301.PubMedPubMedCentral
15.
Zurück zum Zitat Langerak A, Groenen P, Brüggemann M, Beldjord K, Bellan C, Bonello L, et al. EuroClonality/BIOMED-2 guidelines for interpretation and reporting of Ig/TCR clonality testing in suspected lymphoproliferations. Leukemia. 2012;26:2159–71.PubMedCrossRefPubMedCentral Langerak A, Groenen P, Brüggemann M, Beldjord K, Bellan C, Bonello L, et al. EuroClonality/BIOMED-2 guidelines for interpretation and reporting of Ig/TCR clonality testing in suspected lymphoproliferations. Leukemia. 2012;26:2159–71.PubMedCrossRefPubMedCentral
16.
Zurück zum Zitat Shan G-D, Hu F-L, Yang M, Chen H-T, Chen W-G, Wang Y-G, et al. Clonal immunoglobulin heavy chain and T-cell receptor γ gene rearrangements in primary gastric lymphoma. World J Gastroenterol WJG. 2013;19:5727.CrossRef Shan G-D, Hu F-L, Yang M, Chen H-T, Chen W-G, Wang Y-G, et al. Clonal immunoglobulin heavy chain and T-cell receptor γ gene rearrangements in primary gastric lymphoma. World J Gastroenterol WJG. 2013;19:5727.CrossRef
17.
Zurück zum Zitat Van Krieken J, Langerak A, Macintyre E, Kneba M, Hodges E, Sanz RG, et al. Improved reliability of lymphoma diagnostics via PCR-based clonality testing: report of the BIOMED-2 Concerted Action BHM4-CT98-3936. Leukemia. 2006;21:201–6.PubMedCrossRef Van Krieken J, Langerak A, Macintyre E, Kneba M, Hodges E, Sanz RG, et al. Improved reliability of lymphoma diagnostics via PCR-based clonality testing: report of the BIOMED-2 Concerted Action BHM4-CT98-3936. Leukemia. 2006;21:201–6.PubMedCrossRef
18.
Zurück zum Zitat Shin S, Kim AH, Park J, Kim M, Lim J, Kim Y, et al. Analysis of immunoglobulin and T cell receptor gene rearrangement in the bone marrow of lymphoid neoplasia using BIOMED-2 multiplex polymerase chain reaction. Int J Med Sci. 2013;10:1510.PubMedCrossRefPubMedCentral Shin S, Kim AH, Park J, Kim M, Lim J, Kim Y, et al. Analysis of immunoglobulin and T cell receptor gene rearrangement in the bone marrow of lymphoid neoplasia using BIOMED-2 multiplex polymerase chain reaction. Int J Med Sci. 2013;10:1510.PubMedCrossRefPubMedCentral
19.
Zurück zum Zitat Mannu C, Gazzola A, Bacci F, Sabattini E, Sagramoso C, Roncolato F, et al. Use of IGK gene rearrangement analysis for clonality assessment of lymphoid malignancies: a single center experience. Am J Blood Res. 2011;1:167.PubMedPubMedCentral Mannu C, Gazzola A, Bacci F, Sabattini E, Sagramoso C, Roncolato F, et al. Use of IGK gene rearrangement analysis for clonality assessment of lymphoid malignancies: a single center experience. Am J Blood Res. 2011;1:167.PubMedPubMedCentral
20.
Zurück zum Zitat Kim Y, Choi YD, Choi C, Nam J-H. Diagnostic utility of a clonality test for lymphoproliferative diseases in Koreans using the BIOMED-2 PCR assay. Korean J Pathol. 2013;47:458–65.PubMedCrossRefPubMedCentral Kim Y, Choi YD, Choi C, Nam J-H. Diagnostic utility of a clonality test for lymphoproliferative diseases in Koreans using the BIOMED-2 PCR assay. Korean J Pathol. 2013;47:458–65.PubMedCrossRefPubMedCentral
21.
Zurück zum Zitat Ly B, Cotta CV. The utility of the BIOMED-2 primers in the detection of 2 clonal, B-Lymphoproliferative disorders simultaneously involving the same site. Arch Pathol Lab Med. 2013;137:1654–9.PubMedCrossRef Ly B, Cotta CV. The utility of the BIOMED-2 primers in the detection of 2 clonal, B-Lymphoproliferative disorders simultaneously involving the same site. Arch Pathol Lab Med. 2013;137:1654–9.PubMedCrossRef
22.
Zurück zum Zitat Sung J-Y, Kang SY, Kim S-H, Kwon JE, Ko Y-H. Analysis of immunoglobulin gene rearrangement: comparison between BIOMED-2 multiplex PCR and conventional nested PCR. Lab Med Online. 2011;1:195–201.CrossRef Sung J-Y, Kang SY, Kim S-H, Kwon JE, Ko Y-H. Analysis of immunoglobulin gene rearrangement: comparison between BIOMED-2 multiplex PCR and conventional nested PCR. Lab Med Online. 2011;1:195–201.CrossRef
23.
Zurück zum Zitat Payne K, Wright P, Grant JW, Huang Y, Hamoudi R, Bacon CM, et al. BIOMED-2 PCR assays for IGK gene rearrangements are essential for B-cell clonality analysis in follicular lymphoma. Br J Haematol. 2011;155:84–92.PubMedCrossRef Payne K, Wright P, Grant JW, Huang Y, Hamoudi R, Bacon CM, et al. BIOMED-2 PCR assays for IGK gene rearrangements are essential for B-cell clonality analysis in follicular lymphoma. Br J Haematol. 2011;155:84–92.PubMedCrossRef
24.
Zurück zum Zitat Berget E, Helgeland L, Molven A, Vintermyr OK. Detection of clonality in follicular lymphoma using formalin-fixed, paraffin-embedded tissue samples and BIOMED-2 immunoglobulin primers. J Clin Pathol. 2011;64:37–41.PubMedCrossRef Berget E, Helgeland L, Molven A, Vintermyr OK. Detection of clonality in follicular lymphoma using formalin-fixed, paraffin-embedded tissue samples and BIOMED-2 immunoglobulin primers. J Clin Pathol. 2011;64:37–41.PubMedCrossRef
25.
Zurück zum Zitat Halldorsdottir AM, Zehnbauer BA, Burack WR. Application of BIOMED-2 clonality assays to formalin-fixed paraffin embedded follicular lymphoma specimens: superior performance of the IGK assays compared to IGH for suboptimal specimens. Leukemia & lymphoma. 2007;48:1338–43.CrossRef Halldorsdottir AM, Zehnbauer BA, Burack WR. Application of BIOMED-2 clonality assays to formalin-fixed paraffin embedded follicular lymphoma specimens: superior performance of the IGK assays compared to IGH for suboptimal specimens. Leukemia & lymphoma. 2007;48:1338–43.CrossRef
Metadaten
Titel
Evaluation diagnostic usefulness of immunoglobulin light chains (Igκ, Igλ) and incomplete IGH D-J clonal gene rearrangements in patients with B-cell non-Hodgkin lymphomas using BIOMED-2 protocol
Publikationsdatum
01.11.2014
Erschienen in
Clinical and Translational Oncology / Ausgabe 11/2014
Print ISSN: 1699-048X
Elektronische ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-014-1188-4

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.