Patterns and genomic correlates of PD-L1 expression in patients with biliary tract cancers.
Cholangiocarcinoma
bile ducts
extrahepatic
gallbladder cancer (GBC)
immunotherapy
intrahepatic
mutation
Journal
Journal of gastrointestinal oncology
ISSN: 2078-6891
Titre abrégé: J Gastrointest Oncol
Pays: China
ID NLM: 101557751
Informations de publication
Date de publication:
Dec 2019
Dec 2019
Historique:
entrez:
18
1
2020
pubmed:
18
1
2020
medline:
18
1
2020
Statut:
ppublish
Résumé
Patients with biliary tract cancer (BTC) have a dismal prognosis and limited treatment options. Given the potential for immunotherapy in patients with BTC, we studied the expression of programmed death ligand-1 (PD-L1)/programmed death-1 (PD-1) and evaluated for associated genetic alterations in patients with BTC. By immunohistochemistry (IHC), PD-L1 (SP142 antibody; ≥2+ and/or ≥5% staining on tumor cells considered positive) and PD-1 [NAT105 antibody; ≥1+ staining of tumor infiltrating lymphocytes (TILs) considered positive] expression was studied and next-generation sequencing (NGS) was performed using Caris Life Sciences' sequencing panel of 592 genes. A total of 652 patients with BTC were included in this study: 77 extrahepatic cholangiocarcinoma (ECC), 203 gallbladder cancer (GBC), and 372 intrahepatic cholangiocarcinoma (ICC). Of the 652 tumors 8.6% were PD-L1 positive with the following distribution: GBC 12.3% (25/203), ICC 7.3% (27/372), and ECC 5.2% (4/77). There was a statistically significant increase in BRAF, BRCA2, RNF43, and TP53 mutations in PD-L1 positive group as compared to PD-L1 negative. Among other biomarkers tested, TOP2A, tumor mutational burden (TMB) high (≥17 mutations per megabase) (10.7%), and microsatellite instability high (MSI-H) (7.1%) were increased in PD-L1 positive tumors versus PD-L1 negative tumors. PD-L1 expression was noted in a small percentage (8.6%) of patients with BTC. This finding suggests potential benefit of immunotherapy in this subset of patients. Furthermore, there was a statistically significant association between PD-L1 expression and certain genomic alterations (
Sections du résumé
BACKGROUND
BACKGROUND
Patients with biliary tract cancer (BTC) have a dismal prognosis and limited treatment options. Given the potential for immunotherapy in patients with BTC, we studied the expression of programmed death ligand-1 (PD-L1)/programmed death-1 (PD-1) and evaluated for associated genetic alterations in patients with BTC.
METHODS
METHODS
By immunohistochemistry (IHC), PD-L1 (SP142 antibody; ≥2+ and/or ≥5% staining on tumor cells considered positive) and PD-1 [NAT105 antibody; ≥1+ staining of tumor infiltrating lymphocytes (TILs) considered positive] expression was studied and next-generation sequencing (NGS) was performed using Caris Life Sciences' sequencing panel of 592 genes. A total of 652 patients with BTC were included in this study: 77 extrahepatic cholangiocarcinoma (ECC), 203 gallbladder cancer (GBC), and 372 intrahepatic cholangiocarcinoma (ICC).
RESULTS
RESULTS
Of the 652 tumors 8.6% were PD-L1 positive with the following distribution: GBC 12.3% (25/203), ICC 7.3% (27/372), and ECC 5.2% (4/77). There was a statistically significant increase in BRAF, BRCA2, RNF43, and TP53 mutations in PD-L1 positive group as compared to PD-L1 negative. Among other biomarkers tested, TOP2A, tumor mutational burden (TMB) high (≥17 mutations per megabase) (10.7%), and microsatellite instability high (MSI-H) (7.1%) were increased in PD-L1 positive tumors versus PD-L1 negative tumors.
CONCLUSIONS
CONCLUSIONS
PD-L1 expression was noted in a small percentage (8.6%) of patients with BTC. This finding suggests potential benefit of immunotherapy in this subset of patients. Furthermore, there was a statistically significant association between PD-L1 expression and certain genomic alterations (
Identifiants
pubmed: 31949927
doi: 10.21037/jgo.2019.08.08
pii: jgo-10-06-1099
pmc: PMC6955012
doi:
Types de publication
Journal Article
Langues
eng
Pagination
1099-1109Subventions
Organisme : NCI NIH HHS
ID : P50 CA210964
Pays : United States
Informations de copyright
2019 Journal of Gastrointestinal Oncology. All rights reserved.
Déclaration de conflit d'intérêts
Conflicts of Interest: K Mody—Research Support: Agios, Senwha Biosciences, Taiho, ArQule, AstraZeneca, Genentech, Incyte, Tracon Pharmaceuticals, Medimmune, Puma Biotechnology. Consulting: Astra Zeneca, Bayer, Celgene, Eisai, Exelixis, Ipsen, Merrimack, Vicus. M Saul and K Poorman—Employment: Caris Life Sciences. The other authors have no conflicts of interest to declare.
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