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Chung, See, Choi, Min, Cho, and Lee: Comparison of the Rate of Detection of Immunoglobulin Heavy Chain Gene Rearrangement by Fluoresecence In Situ Hybridization Probes in Multiple Myeloma
Original Article

Korean J Leg Med 2006;26(5):317-322.

Published online: 10 February 2006

DOI: https://doi.org/10.3343/kjlm.2006.26.5.317

Comparison of the Rate of Detection of Immunoglobulin Heavy Chain Gene Rearrangement by Fluoresecence In Situ Hybridization Probes in Multiple Myeloma

Hye Yoon Chung, M.D., Cha Ja See, M.T., Jung Eun Choi, M.T., Hyun Jung Min, M.S., Han Ik Cho, M.D., Dong Soon Lee, M.D.

Department of Laboratory Medicine, College of Medicine, Seoul National University, Seoul, Korea

Received 2 June 2006       Revised 21 August 2006       Accepted 23 August 2006

Copyright © 2006 The Korean Society for Legal Medicine

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Immunoglobulin heavy chain (IgH) gene rearrangement, which is frequently observed in multiple myeloma, can now be detected easily by using a fluorescence in situ hybridization (FISH) method. The aim of this study was to determine the detection rate and compare the utility of the three most commonly used probes: IGH/CCND1 dual color, dual fusion probe; IGH/BCL2 dual color, dual fusion probe; and IGH dual color break apart rearrangement probe; all from Vysis Products (Downers Grove, IL, USA).

Methods

From October 1994 to July 2003, 99 patients were diagnosed as multiple myeloma at Seoul National University Hospital, Asan Medical Center and Gachon University Gil hospital. We applied the three different probes of IgH FISH on bone marrow specimens from the 99 Korean patients with multiple myeloma to detect IgH gene rearrangement.

Results

Forty-one (41.4%) of the 99 patients had IgH gene rearrangement. Of those 41 patients, 23 (56.1%) showed positive to all three probes, but the remaining 18 (43.9%) showed a discrepancy between the three probes: 13 (72.2%) of the 18 patients were only positive to the IGH dual color break apart rearrangement probe and the detection rate was 39.6% on the average.

Conclusions

These results demonstrate that IGH dual color break apart rearrangement probe is superior to the other two probes in qualitative and quantitative ways. Thus, we recommend IGH dual color break apart rearrangement probe for the diagnosis and monitoring of multiple myeloma.

Keywords: Immunoglobulin heavy chain gene rearrangement, FISH, Multiple myeloma

References

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Table 1.
Comparison of the results of IGH/CCND1, IGH/BCL2 and IGH break apart rearrangement probes in patients with multiple myeloma
FISH Probe N. (%) of patients positive (N=99)
IGH/CCND1 28 (28.3%)
IGH/BCL2 23 (23.2%)
IGH break apart probe 41 (41.4%)
Table 2.
Results of FISH by 3 kinds of probes involving IgH gene in patients with multiple myeloma
IGH break apart IGH/CCND1 IGH/BCL2 N. of patients positive (N=99)
+ − − 13
− + − 0
− − + 0
+ + + 23
+ + − 5
+ − + 0
− − − 58
Table 3.
Proportion of cells with a positive signal to each probe among 200 bone marrow nucleated cells in patients with multiple myeloma
Case No. (N=23) IGH/CCND1 (%) IGH/BCL2 (%) IGH break apart rearrangement (%)
1 75.0 98.0 84.0
2 40.0 24.5 30.0
3 18.0 20.5 12.0
4 11.0 9.5 21.5*
5 79.0 48.0 80.5*
6 80.5 85.0 100.0*
7 27.5 17.0 20.0
8 18.0 11.5 15.0
9 60.0 80.0 95.0*
10 62.0 85.0 86.0*
11 16.5 19.0 28.0*
12 40.0 48.0 12.0
13 22.0 28.0 25.5
14 12.0 5.0 15.5*
15 13.5 15.0 14.5
16 25.0 10.0 21.0
17 3.0 8.0 30.0*
18 9.0 10.0 12.0*
19 70.0 56.0 62.5
20 65.0 48.5 71.0*
21 29.0 17.0 70.3*
22 52.0 18.0 54.0*
23 47.0 10.0 17.5
Mean 38.1 33.5 42.5

* bold, The quantitative results with IGH break apart rearrangement probe higher than those with the other probes.

Table 4.
Quantitative results of 13 cases showing IgH rearrangement only by IGH break apart rearrangement probe
No of case (N=13) IGH/CCND1 (%) IGH/BCL2 (%) IGH break apart rearrangement (%)
1 0.0 0.0 34.5
2 0.0 0.0 51.0
3 0.0 0.0 38.0
4 0.0 0.0 44.5
5 0.0 0.0 26.0
6 0.0 0.0 17.5
7 0.0 0.0 30.5
8 0.0 0.0 23.5
9 0.0 0.0 38.0
10 0.0 0.0 61.5
11 0.0 0.0 67.0
12 0.0 0.0 29.5
13 0.0 0.0 53.0
Mean 0.0 0.0 39.6
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