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JMD 2002, Vol. 4, No. 3
Copyright © 2002 American Society for Investigative Pathology & Association for Molecular Pathology

Rapid Detection of IgH/BCL2 Rearrangement in Follicular Lymphoma by Interphase Fluorescence in Situ Hybridization with Bacterial Artificial Chromosome Probes

Feng Jiang*, Fan Lin{dagger}, Roger Price*, Jun Gu*, L. Jeffrey Medeiros{ddagger}, Hua Z. Zhang*, Su-Su Xie*, Nancy P. Caraway* and Ruth L. Katz*

From the Departments of Pathology * and Hematopathology, {ddagger} The University of Texas M. D. Anderson Cancer Center, Houston, Texas; and the Department of Pathology, {dagger} Geisinger Medical Center, Danville, Pennsylvania

Follicular lymphomas (FLs) can be difficult to diagnose on aspirated specimens since the architectural pattern is not present. FLs characteristically have rearrangements in the IgH and BCL2 genes resulting from the reciprocal t(14;18) (q32; q21) translocation. Because of the dispersed distribution of breakpoints, fluorescence in situ hybridization (FISH) using genomic probes that span or flank the breakpoints is ideal for detecting this rearrangement in fine-needle aspiration (FNA) biopsies. To develop a set of probes, a bacterial artificial chromosome library was screened and the clones were mapped by fiber FISH. The probes were produced by the direct incorporation of fluorochrome-labeled nucleotides. The colocalization base FISH assay was applied to Cytospin preparations from FNA biopsies of lymph nodes from 26 patients with FL and 10 patients without FL. In those with FL, the percentage of cells with at least one IgH/BCL2 fusion signal ranged from 22% to 100% (mean, 63%), which was statistically significantly higher than that in FL-negative samples (mean, 2.7%). The probes demonstrated a significantly lower cutoff value (7%) in normal controls and effectively reduced the false-positive rate in FL-negative cases. These results were confirmed with fiber FISH assays on the same specimens. This interphase FISH assay is rapid and reliable for detecting rearrangements in the IGH/BCL2 gene, thereby aiding in the diagnosis of FL on FNA biopsy specimens.




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