Detection of immunoglobulin heavy chain gene rearrangements in classic hodgkin lymphoma using commercially available BIOMED-2 primers.
BACKGROUND
Classic Hodgkin lymphoma (cHL) is regarded as a clonal B-cell neoplasm. The BIOMED-2 group recently validated a set of immunoglobulin heavy chain (IGH) multiplex primers with high sensitivity in B-cell non-Hodgkin lymphomas. We postulated that after using these primers, a higher proportion of the cHLs would have detectable rearrangements without microdissection.


METHODS
Forty-two patients with cHL were selected. The densities of Reed-Sternberg cells/10 high-power field and CD30+ cells/10 high-power field were classified as low, intermediate, or high. The quantities of background CD20+ B cells were classified as low or high. DNA from formalin-fixed, paraffin-embedded sections was used to perform polymerase chain reactions with the InVivoScribe IGH Gene Clonality Assay for ABI detection. Dominant peaks were considered to be monoclonal if they were >3x the height of the polyclonal background, and borderline monoclonal if between 2 and 3x.


RESULTS
Overall, 10/42 (24%) of the cHL samples were monoclonal, and 7/42 (17%) were borderline monoclonal. Higher densities of CD30+ cells and lower background B cells were statistically correlated with clonality.


CONCLUSIONS
The BIOMED-2 primers demonstrate IGH gene clonality in 24% to 40% of cHLs without microdissection. In a subset of the cHL, the IGH gene rearrangement analysis might be useful for diagnosis, but can lead to confusion between cHLs and non-Hodgkin lymphomas if used as a discriminative criterion.
Chute
Deborah J
DJ
Department of Pathology, University of Virginia Health System, Charlottesville, VA 22908, USA. dchute@stanford.edu
Cousar
John B
JB
Mahadevan
Mani S
MS
Siegrist
Karen A
KA
Silverman
Lawrence M
LM
Stoler
Mark H
MH
D000293:Adolescent; D000328:Adult; D000368:Aged; D018951:Antigens, CD20 / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D002452:Cell Count; D002648:Child; D002999:Clone Cells; D017931:DNA Primers / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics*; D003937:Diagnosis, Differential; D005260:Female; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain / Q000235:genetics*; D006689:Hodgkin Disease / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D017730:Ki-1 Antigen / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D016539:Reed-Sternberg Cells / Q000378:metabolism / Q000473:pathology
D018951:Antigens, CD20; D014408:Biomarkers, Tumor; D017931:DNA Primers; D004273:DNA, Neoplasm; D007143:Immunoglobulin Heavy Chains; D017730:Ki-1 Antigen