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<p>Genomic imbalance at 9p24.1 locus, the chromosome region that maps <i>PD-L1</i> and <i>PD-L-2</i> (<i>programmed death ligand 1 and 2</i>) genes, is a recurrent alteration in classic Hodgkin lymphoma (cHL). We analyzed 9p24.1 imbalance by fluorescence in situ hybridization assay on formalin-fixed paraffin-embedded biopsies of 28 patients with newly diagnosed cHL to characterize the genetic profiles. Results were correlated with PD-L1 (H-score) and LMP-1 (<i>latent membrane protein 1</i>) protein expression of Epstein-Barr virus by immunohistochemistry and clinical features. Genomic alterations in Hodgkin/Reed Sternberg (H/RS) cells were classified as amplification, copy gain, and polysomy. Three molecular cytogenetic groups were defined according to the type and frequency of the copy number alteration: Group A (with amplification) 32%, Group G (with &gt; 50% cells with copy gains but without amplification) 36%, and Group P (with ≥ 50% cells with polysomies but without amplification) 32%. A different frequency of copy gains (<i>p</i> = 0.02) and polysomies (<i>p</i> ≤ 0.01) among groups was found. A negative correlation between the percentage of H/RS cells with polysomies and the PD-L1 protein expression (<i>p</i> ≤ 0.01) was observed. Tumor microenvironmental cells showed chromosome 9 monosomy particularly associated to Group P. The highest H-score mean value was observed in Group A (265.6), while Groups G and P showed 123 and 60.3 H-score, respectively. Group P showed the highest mean age (<i>p</i> = 0.036) and increased frequency of advanced stages, B symptoms, and extranodal involvement, while Groups A and G were associated with localized stages (<i>p</i> = 0.035) and bulky mass, highlighting the importance of 9p24.1 genomic imbalance profile in the biological characterization of cHL.</p>

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PD-L1/PD-L2 genetic profile in the molecular cytogenetic classification of classic Hodgkin lymphoma

  • 期刊论文

  • 发表日期：

    2025年2月20日

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  • Mauro García-Montenegro,
  • Marina Narbaitz,
  • María Fernanda Metrebian,
  • Astrid Pavlovsky,
  • Irma Slavutsky

摘要

Genomic imbalance at 9p24.1 locus, the chromosome region that maps PD-L1 and PD-L-2 (programmed death ligand 1 and 2) genes, is a recurrent alteration in classic Hodgkin lymphoma (cHL). We analyzed 9p24.1 imbalance by fluorescence in situ hybridization assay on formalin-fixed paraffin-embedded biopsies of 28 patients with newly diagnosed cHL to characterize the genetic profiles. Results were correlated with PD-L1 (H-score) and LMP-1 (latent membrane protein 1) protein expression of Epstein-Barr virus by immunohistochemistry and clinical features. Genomic alterations in Hodgkin/Reed Sternberg (H/RS) cells were classified as amplification, copy gain, and polysomy. Three molecular cytogenetic groups were defined according to the type and frequency of the copy number alteration: Group A (with amplification) 32%, Group G (with > 50% cells with copy gains but without amplification) 36%, and Group P (with ≥ 50% cells with polysomies but without amplification) 32%. A different frequency of copy gains (p = 0.02) and polysomies (p ≤ 0.01) among groups was found. A negative correlation between the percentage of H/RS cells with polysomies and the PD-L1 protein expression (p ≤ 0.01) was observed. Tumor microenvironmental cells showed chromosome 9 monosomy particularly associated to Group P. The highest H-score mean value was observed in Group A (265.6), while Groups G and P showed 123 and 60.3 H-score, respectively. Group P showed the highest mean age (p = 0.036) and increased frequency of advanced stages, B symptoms, and extranodal involvement, while Groups A and G were associated with localized stages (p = 0.035) and bulky mass, highlighting the importance of 9p24.1 genomic imbalance profile in the biological characterization of cHL.