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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

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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 D–J 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.

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Abbreviations

B-NHL:

B-cell non-Hodgkin lymphomas

SHM:

Somatic hypermutation

IgH :

Immunoglobulin heavy chain

(V):

Variable

(D):

Diversity

(J):

Joining

Igκ :

Immunoglobulin kappa

Igλ :

Immunoglobulin lambda

IGH D–J :

Incomplete immunoglobulin heavy chain (D-J)

FFPE:

Formalin-fixed, paraffin-embedded

FL:

Follicular lymphoma

DLBCL:

Diffuse large B-cell lymphoma

MCL:

Mantle cell lymphoma

Ig/TCR:

Immunoglobulin and T cell receptor

BIOMED-2:

European Biomedicine and Health

WHO:

World Health Organization

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Acknowledgments

This study was supported by the Iran National Science Foundation (INSF, Grant No: 87041113) and we gratefully acknowledge Dr S Dastmalchi from Biotechnology Research Center, Tabriz University of Medical Sciences, who helped in this study.

Conflict of interest

The authors declared no conflict of interest.

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Authors and Affiliations

  1. Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran

    S. Ghorbian & G. R. Javadi

  2. Department of Medical Genetics, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

    E. Sakhinia

  3. Department of Pathology, Imam Khomeini Hospital Complex, Medical Sciences / University of Tehran, Tehran, Iran

    I. Jahanzad

Authors
  1. S. Ghorbian
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  2. I. Jahanzad
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  3. G. R. Javadi
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  4. E. Sakhinia
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Corresponding authors

Correspondence to G. R. Javadi or E. Sakhinia.

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Ghorbian, S., Jahanzad, I., Javadi, G.R. et al. 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. Clin Transl Oncol 16, 1006–1011 (2014). https://doi.org/10.1007/s12094-014-1188-4

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  • DOI: https://doi.org/10.1007/s12094-014-1188-4

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