Diagnostic value of immunoglobulin κ light chain gene rearrangement analysis in B-cell lymphomas

Kokovic,Ira; Jezersek Novakovic,Barbara; Novakovic,Srdjan

doi:10.3892/ijo.2014.2790

Diagnostic value of immunoglobulin κ light chain gene rearrangement analysis in B-cell lymphomas

Authors:
- Ira Kokovic
- Barbara Jezersek Novakovic
- Srdjan Novakovic
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Affiliations: Department of Molecular Diagnostics, Institute of Oncology Ljubljana, Ljubljana, Slovenia, Division of Medical Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia
Published online on: December 9, 2014 https://doi.org/10.3892/ijo.2014.2790
Pages: 953-962
Copyright: © Kokovic et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Analysis of the immunoglobulin κ light chain (IGK) gene is an alternative method for B-cell clonality assessment in the diagnosis of mature B-cell proliferations in which the detection of clonal immunoglobulin heavy chain (IGH) gene rearrangements fails. The aim of the present study was to evaluate the added value of standardized BIOMED-2 assay for the detection of clonal IGK gene rearrangements in the diagnostic setting of suspected B-cell lymphomas. With this purpose, 92 specimens from 80 patients with the final diagnosis of mature B-cell lymphoma (37 specimens), mature T-cell lymphoma (26 specimens) and reactive lymphoid proliferation (29 specimens) were analyzed for B-cell clonality. B-cell clonality analysis was performed using the BIOMED-2 IGH and IGK gene clonality assays. The determined sensitivity of the IGK assay was 67.6%, while the determined sensitivity of the IGH assay was 75.7%. The sensitivity of combined IGH+IGK assay was 81.1%. The determined specificity of the IGK assay was 96.2% in the group of T-cell lymphomas and 96.6% in the group of reactive lesions. The determined specificity of the IGH assay was 84.6% in the group of lymphomas and 86.2% in the group of reactive lesions. The comparison of GeneScan (GS) and heteroduplex pretreatment-polyacrylamide gel electrophoresis (HD-PAGE) methods for the analysis of IGK gene rearrangements showed a higher efficacy of GS analysis in a series of 27 B-cell lymphomas analyzed by both methods. In the present study, we demonstrated that by applying the combined IGH+IGK clonality assay the overall detection rate of B-cell clonality was increased by 5.4%. Thus, we confirmed the added value of the standardized BIOMED-2 IGK assay for assessment of B-cell clonality in suspected B-cell lymphomas with inconclusive clinical and cyto/histological diagnosis.

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1	Diss TC, Peng H, Wotherspoon AC, Isaacson PG and Pan L: Detection of monoclonality in low-grade B-cell lymphomas using the polymerase chain reaction is dependent on primer selection and lymphoma type. J Pathol. 169:291–295. 1993. View Article : Google Scholar : PubMed/NCBI
2	McCarthy KP, Sloane JP and Wiedemann LM: Rapid method for distinguishing clonal from polyclonal B cell populations in surgical biopsy specimens. J Clin Pathol. 43:429–432. 1990. View Article : Google Scholar : PubMed/NCBI
3	Trainor KJ, Brisco MJ, Wan JH, Neoh S, Grist S and Morley AA: Gene rearrangement in B- and T-lymphoproliferative disease detected by the polymerase chain reaction. Blood. 78:192–195. 1991.PubMed/NCBI
4	Amara K, Trimeche M, Ziadi S, Sriha B, Mokni M and Korbi S: PCR-based clonality analysis of B-cell lymphomas in paraffin-embedded tissues: diagnostic value of immunoglobulin k and l light chain gene rearrangement investigation. Pathol Res Pract. 202:425–431. 2006. View Article : Google Scholar
5	Gameiro P, Sebastião M, Spetalen S, Gomes da Silva M and Cabeçadas J: The added value of immunoglobulin Kappa light chain gene (IGK) rearrangement analysis in suspected B-cell lymphomas: three illustrative cases. J Hematopathol. 5:45–56. 2012. View Article : Google Scholar
6	Liu H, Bench AJ, Bacon CM, Payne K, Huang Y, Scott MA, et al: A practical strategy for the routine use of BIOMED-2 PCR assays for detection of B- and T-cell clonality in diagnostic haematopathology. Br J Haematol. 138:31–43. 2007. View Article : Google Scholar : PubMed/NCBI
7	Payne K, Wright P, Grant JW, Huang Y, Hamoudi J, 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. 155:84–92. 2011. View Article : Google Scholar : PubMed/NCBI
8	Berget E, Helgeland L, Molven A and Vintermyr OK: Detection of clonality in follicular lymphoma using formalin-fixed, paraffin-embedded tissue samples and BIOMED-2 immunoglobulin primers. J Clin Pathol. 64:37–41. 2011. View Article : Google Scholar
9	Diss TC, Liu HX, Du MQ and Isaacson PG: Improvements to B cell clonality analysis using PCR amplification of immunoglobulin light chain genes. Mol Pathol. 55:98–101. 2002. View Article : Google Scholar : PubMed/NCBI
10	Evans PA, Pott C, Groenen PJ, 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. 21:207–214. 2007. View Article : Google Scholar
11	Langerak AW, Nadel B, De Torbal A, Wolvers-Tettero IL, van Gastel-Mol EJ, Verhaaf B, et al: Unraveling the consecutive recombination events in the human IGK locus. J Immunol. 173:3878–3888. 2004. View Article : Google Scholar : PubMed/NCBI
12	van der Burg M, Tumkaya T, Boerma M, de Bruin-Versteeg S, Langerak AW and van Dongen JJ: Ordered recombination of immunoglobulin light chain genes occurs at the IGK locus but seems less strict at the IGL locus. Blood. 97:1001–1008. 2001. View Article : Google Scholar : PubMed/NCBI
13	Pai RK, Chakerian AE, Binder JM, Amin M and Viswanatha DS: B-cell clonality determination using an immunoglobulin k light chain polymerase chain reaction method. J Mol Diagn. 7:300–307. 2005. View Article : Google Scholar : PubMed/NCBI
14	Catherwood MA, Gonzales D, Patton C, Dobbin E, Venkatraman L and Alexander HD: Improved clonality assessment in germinal centre/post germinal centre non-Hodgkin’s lymphomas with high rates of somatic hypermutation. J Clin Pathol. 60:524–528. 2007. View Article : Google Scholar
15	Kokovic I, Jezersek Novakovic B, Cerkovnik P and Novakovic S: Clonality analysis of lymphoid proliferations using the BIOMED-2 clonality assays: a single institution experience. Radiol Oncol. 48:155–162. 2014. View Article : Google Scholar : PubMed/NCBI
16	Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, et al: WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues. IARC Press; Lyon: 2008
17	Mannu C, Gazzola A, Bacci F, Sabattini E, Sagramoso C and Roncolato F: Use of IGK gene rearrangement analysis for clonality assessment of lymphoid malignancies: a single center experience. Am J Blood Res. 1:167–174. 2011.PubMed/NCBI
18	van Krieken JH, Langerak AW, Macintyre EA, Kneba M, Hodges E, Garcia Sanz R, et al: Improved reliability of lymphoma diagnostics via PCR-based clonality testing: report of the BIOMED-2 concerted action BHM4-CT98-3936. Leukemia. 21:201–206. 2007. View Article : Google Scholar
19	Langerak AW, Groenen PJ, 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. 26:2159–2171. 2012. View Article : Google Scholar : PubMed/NCBI
20	van Dongen JJ, Langerak AW, Brüggemann M, Evans PA, Hummel M, Lavender FL, et al: Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptore gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BHM4-CT98-3936. Leukemia. 17:2257–2317. 2003. View Article : Google Scholar : PubMed/NCBI
21	Brüggemann M, White H, Gaulard P, Garcia-Sanz R, Gameiro P, Oeschger S, et al: Powerful strategy for polymerase chain reaction-based clonality assessment in T-cell malignancies. Report of the BIOMED-2 Concerted Action BHM4-CT98-3936. Leukemia. 21:215–221. 2007. View Article : Google Scholar
22	Langerak AW, Molina TJ, Lavender FL, Pearson D, Flohr T, Sambade C, et al: Polymerase chain reaction-based clonality testing in tissue samples with reactive lymphoproliferations: usefulness and pitfalls. A report of the BIOMED-2 Concerted Action BHM4-CT98-3936. Leukemia. 21:222–229. 2007. View Article : Google Scholar