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Frequent Copy Number Gain of Genes for PD-1 Ligands in Squamous Cell Carcinoma of the Cervix or Vulva

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Key Points

  • Cogain or coamplification was found in 67% of cervical and 43% of vulvar cases of squamous cell carcinoma, in a recent study.
  • PD-L1 expression was highest in cases of coamplification and lowest in disomy cases.

In a study reported in JAMA Oncology, Howitt et al identified copy number gain of genes encoding programmed cell death protein 1 (PD-1) ligands in a sizable proportion of patients with squamous cell carcinoma of the cervix or vulva.

Study Details

The study involved fluorescence in situ hybridization targeting of CD274 (encoding PD-1 ligand 1 [PD-L1]) and PDCD1LG2 (encoding PD-1 ligand 2 [PD-L2]) and the centromere region of chromosome 9 in formalin-fixed, paraffin-embedded biopsy specimens from 48 patients with cervical squamous cell carcinoma and 23 patients with vulvar squamous cell carcinoma from archives at Brigham and Women’s Hospital.

Copy Number Gain

Cogain or coamplification of CD274 and PDCD1LG2 at 9p24.1 was found in 32 (67%, coamplification in 11) of 48 cervical squamous cell carcinomas and in 10 (43%, coamplification in 6) of 23 vulvar squamous cell carcinomas. Of the cervical squamous cell carcinomas, 19% of cases showed polysomy, and 15% of cases showed disomy. Of the vulvar squamous cell carcinomas, 26% showed polysomy, and 30% showed disomy. For both cervical and vulvar squamous cell carcinomas, median PD-L1 expression reflected the degree of genetic abnormality, with the highest levels in cases of coamplification, followed by cogain, polysomy, and disomy.

The investigators concluded: “Recurrent copy number gain of the genes encoding the PD-1 ligands provides a genetic basis for PD-L1 expression in a subset of cervical and vulvar squamous cell carcinomas and identifies a class of patients that are rational candidates for therapies targeting PD-1.”

The study was supported by the Dana-Farber Cancer Institute, the International Immuno-Oncology Network sponsored by Bristol-Myers-Squibb, and the National Institutes of Health.

Scott J. Rodig, MD, PhD, of Brigham and Women’s Hospital, is the corresponding author of the JAMA Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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