International Journal of Hematology

, Volume 78, Issue 2, pp 154–159 | Cite as

Fluorescence In Situ Hybridization Detection of Chromosome IGH/BCL2 Translocations from Paraffin-Embedded Tissue: Evaluation in Follicular Lymphoma

  • Yuko Hirose
  • Yasufumi Masaki
  • Mamoru Ozaki


Follicular lymphoma is categorized as low-grade lymphoma because of the long median survival, but the disease is difficult to cure because of frequent recurrence. The t(14;18)(q32;q21) associated with follicular lymphoma juxtaposes a portion of BCL-2 (18q21) and IGH(14q32); the result is bcl-2 overexpression. In this study, a highly sensitive 2-color fluorescence in situ hybridization (FISH) method was used to detect t(14;18)(q32;q21) in the nuclei of paraffin-embedded tissue sections. Fourteen specimens, including 11 samples from follicular lymphoma and 3 samples from diffuse large cell lymphoma, for which results of karyotype study and paraffin-embedded tissues were available were selected for FISH study. The FISH results were compared with results of karyotype study of the lymph nodes involved in lymphoma. Among our 11 patients with the diagnosis of follicular lymphoma in whom karyotype study was performed, 8 had t(14;18)(q32;q21) in karyotype analysis, and 7 of these patients had a positive pattern in FISH analysis. In 1 case, FISH analysis was difficult because of weak signals. All 3 patients with diffuse large cell lymphoma and t(14;18)(q32;q21) in karyotype analysis had a positive pattern in FISH analysis. In 3 cases of follicular lymphoma without t(14;18)(q32;q21) in karyotype analysis, FISH did not show a positive pattern. Therefore the FISH assay in tissue was found to be very sensitive in detection of IGH/BCL2 translocation and was helpful in diagnosis of follicular lymphoma or in clarification of the cell origin of lymphoma when karyotype analysis was not available. Performing FISH on paraffin sections also is useful because we can identify cells with genetic abnormalities in the tumor and make a retrospective cytogenetic diagnosis even with old paraffin-embedded specimens. Int J Hematol. 2003;78:154-159.

Key words

FISH IGH/BCL2 Follicular lymphoma 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Greer JP, Macon WR, McCurley TL. Follicular center cell lymphomas. In: Lee GR, Foerster J, Lukens J, et al, eds.Wintrobe’s Clinical Hematology. 10th ed. Baltimore:Williams & Wilkins; 1999:2472–2474.Google Scholar
  2. 2.
    Tsujimoto Y, Jaffe E, Cossman J, Gorham J, Nowell PC, Croce CM. Clustering of breakpoints on chromosome 11 in human B-cell neoplasms with the t(11;14) chromosome translocation.Nature. 1985;315:340–343.CrossRefPubMedGoogle Scholar
  3. 3.
    Tsujimoto Y, Croce CM. Analysis of the structure, transcripts, and protein products of bcl-2, the gene involved in human follicular lymphoma.Proc Natl Acad Sci U S A. 1986;83:5214–5218.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Cleary ML, Smith SD, Sklar J. Cloning and structural analysis of cDNAs for bcl-2 and a hybrid bcl-2/immunoglobulin transcript resulting from the t(14;18) translocation.Cell. 1986;47:19–28.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    McKeithan TW. Molecular biology of non-Hodgkin’s lymphomas.Semin Oncol. 1990;17:30–42.PubMedGoogle Scholar
  6. 6.
    Erikson J, Finan J, Tsujimoto Y, Nowell PC, Croce CM. The chromosome 14 breakpoint in neoplastic B cells with the t(11;14) translocation involves the immunoglobulin heavy chain locus.Proc Natl Acad Sci U S A. 1984;81:4144–4148.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Macintyre EA, Delabesse E. Molecular approaches to the diagnosis and evaluation of lymphoid malignancies.Semin Hematol. 1999; 36:373–389.PubMedGoogle Scholar
  8. 8.
    Rack KA, Salomon-Nguyen F, Radford-Weiss I, et al. FISH detec tion of chromosome 14q32/IgH translocations: evaluation in follicular lymphoma.Br J Haematol. 1998;103:495–504.CrossRefPubMedGoogle Scholar
  9. 9.
    Nathwani BN, Piris MA, Harris NL, et al. Follicular lymphoma. In: Jaffe ES, Harris NL, Stein H, Vardiman JW, eds.World Health Organization Classification of Tumours: Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC Press; 2001:162–167.Google Scholar
  10. 10.
    Vaandrager JW, Schuuring E, Kluin-Nelemans HC, Dyer MJS, Raap AK, Kluin PM. DNA fiber fluorescence in situ hybridization analysis of immunoglobulin class switching in B-cell neoplasia: aberrant CH gene rearrangements in follicle center-cell lymphoma.Blood. 1998;92:2871–2878.PubMedGoogle Scholar
  11. 11.
    Remstein ED, Kurtin PJ, Buno I, et al. Diagnostic utility of fluorescence in situ hybridization in mantle-cell lymphoma.Br J Haematol. 2000;110:856–862.CrossRefPubMedGoogle Scholar
  12. 12.
    Huang JZ, Sanger WG, Greiner TG, et al. The t(14;18) defines a unique subset of diffuse large B-cell lymphoma with a germinal center B-cell gene expression profile.Blood. 2002;99:2285–2290.CrossRefPubMedGoogle Scholar
  13. 13.
    Zhang Y, Cheung ANY, Chan ACL, et al. Detection of trisomy 3 in primary gastric B-cell lymphoma by using chromosome in situ hybridization on paraffin sections.Am J Clin Pathol. 1996;9:995–1000.Google Scholar
  14. 14.
    Blanco R, Lyda M, Dabis B, Kraus M, Fenoglio-Preiser C. Trisomy 3 in gastric lymphomas of extranodal marginal zone B-cell (mucosa-associated lymphoid tissue) origin demonstrated by FISH in intact paraffin tissue sections.Hum Pathol. 1999;30:706–711.CrossRefPubMedGoogle Scholar
  15. 15.
    Nomura K, Sekoguchi S, Ueda K, et al. Differentiation of follicular from mucosa-associated lymphoid tissue lymphoma by detection of t(14;18) on single-cell preparations and paraffin-embedded sections.Gene Chromosome Cancer. 2002;33:213–216.CrossRefGoogle Scholar
  16. 16.
    Nomura K, Yoshino T, Nakamura S, et al. Detection of t(11;18) (q21;q21) in marginal zone lymphoma of mucosa-associated lymphatic tissue type on paraffin-embedded tissue sections by using fluorescence in situ hybridization.Cancer Genet Cytogenet. 2003; 140:49–54.CrossRefPubMedGoogle Scholar
  17. 17.
    Horsman DE, Gascoyne RD, Coupland RW, et al. Comparison of cytogenetic analysis, Southern analysis, and polymerase chain reaction for the detection of t(14;18) in follicular lymphoma.Am J Clin Pathol. 1998;103:472–478.CrossRefGoogle Scholar
  18. 18.
    Weiss LM, Warnke RA, Sklar J, et al. Molecular analysis of the t(14;18) chromosomal translocation in malignant lymphoma.N Engl J Med. 1987;317:1185–1189.CrossRefPubMedGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2003

Authors and Affiliations

  1. 1.Division of Hematology and Immunology Department of Internal MedicineKanazawa Medical UniversityIshikawaJapan
  2. 2.Division of Human GeneticsMedical Research Institute of Kanazawa Medical UniversityIshikawaJapan

Personalised recommendations