PD-1 Ligands Implicated In Cervical, Vulvar SCC

Increased expression of programmed death ligand 1 and 2 is detected in cervical and vulvar squamous cell carcinoma patients

medwireNews: Preliminary research points to a potential role for programmed death ligand 1 and 2 expression in the development of Squamous cell carcinoma (SCC) of the cervix or vulva.

Tissue samples revealed that a significant proportion of cervical and vulvar SCC patients had alterations of the CD274 and PDCD1LG2 genes, known to encode the programmed cell death protein 1 (PD-1) ligands, programmed death ligand (PD-L)1 and PD-L2, respectively.

Scott Rodig, from Brigham and Women’s Hospital in Boston, Massachusetts, USA, and co-workers used next-generation sequencing (NGS) to detect copy number gains of the two genes at chromosome 9p24.1 in 12.5% of 24 cervical cases.

There was a high level of co-Amplification in 96% of tumour cells, with up to 15 copies of both genes, and co-gain of the two genes occurred in 4%.

Immunohistochemistry showed “robust” expression of PD-L1 in 95% of tumour cells and further examination of 48 cervical SCCs showed co-amplification or cogain of the two genes in 67%. Specifically, 19% were polysomic and 15% disomic for chromosome 9.

Analysis of 23 vulvar SCCs showed co-amplification of the genes in 26%, cogain in 17%, Polysomy in 26% and disomy in 30%.

And immunohistochemistry for both the cervical and vulvar SCC specimens showed that the highest PD-L1 protein expression occurred in patients with co-amplification, with the lowest expression in cervical samples with disomy, while expression fell with decreasing genetic complexity in vulvar cases.

“Our data reveal that selective copy number gain of CD274 and PDCD1LG2 at 9p24.1 occurs frequently in SCCs of the cervix and vulva and provides a genetic basis for increased PD-L1 protein expression in these tumour types”, the researchers summarise in JAMA Oncology.

The researchers note that 9p24.1 copy number gain has also been detected in Hodgkin lymphoma patients and that Epstein–Barr viral infection may play a role in PD-1 ligand expression.

However, as just 30% of the vulvar SCCs tested positive for p16, a surrogate Biomarker for high-risk human papillomavirus infection,the team writes that the “data presentedhere suggest that 9p24.1 Gene copy number alterations are amajor mechanism of increased PD-L1 expression in SCCs ofthe cervix and vulva, irrespective of viral infection.”

References

Howitt BE, Sun HH, Roemer MGM, et al. Genetic basis for PD-L1 expression in squamous cell carcinomas of the cervix and vulva. JAMA Oncol 2016; Advance online publication 25 February. doi:10.1001/jamaoncol.2015.6326

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