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Programmed cell death ligand 1 (PD-L1, CD274) in cholangiocarcinoma - correlation with clinicopathological data and comparison of antibodies.
- Source :
-
BMC cancer [BMC Cancer] 2019 Jan 15; Vol. 19 (1), pp. 72. Date of Electronic Publication: 2019 Jan 15. - Publication Year :
- 2019
-
Abstract
- Background: Cholangiocarcinoma (CCA) may arise in the intra- or extrahepatic biliary tract and is associated with a poor prognosis. Despite recent advances, to date there is still no established targeted therapeutic approach available. Non-surgical therapeutic agents are urgently needed, as most patients are non-eligible to surgical resection. Anti-PD-L1 therapy prevents cancer cells from evading the immune system and has emerged as a new treatment option in several cancer entities. Recently, PD-L1 expression has been analyzed in comparably small CCA patient cohorts. However, a systematic validation of different PD-L1 antibodies has not been performed in CCA so far.<br />Methods: We stained a tissue microarray consisting of 170 patients, including 72 intrahepatic cholangiocarcinomas (iCCAs), 57 perihilar cholangiocarcinomas (pCCAs) and 41 distal cholangiocarcinomas (dCCAs) by immunohistochemistry and evaluated PD-L1 positivity in tumor and stromal cells. We analyzed three different PD-L1 antibodies (clones 28-8, SP142, and SP263) that are frequently used and recommended for predictive diagnostic testing in other cancer types.<br />Results: For PD-L1 antibody clone SP263, 5% of iCCAs, 4% of pCCAs and 3% of dCCAs exhibited PD-L1 expression on tumor cells, thereby showing the highest frequencies of PD-L1 positivity. Accordingly, highest PD-L1 positivity rates of stromal cells with 31% in iCCA, 40% in pCCA and 61% in dCCA were detected for clone SP263. Agreement of PD-L1 positivity in tumor cells was moderate for clone 28-8 and SP263 (κ = 0.44) and poor between 28-8 and SP142 (κ = 0.13), as well as  SP142 and SP263 (κ = 0.11), respectively. Statistical analyses of PD-L1 expression (clone SP263) on tumor cells with clinicopathological data revealed a positive correlation with shortened overall survival in CCA patients.<br />Conclusions: Selection of appropriate PD-L1 antibodies and careful evaluation of immunohistochemical staining patterns have a significant impact on PD-L1 testing in CCA. Clinical trials are necessary to investigate the putative beneficial effects of PD-L1 targeted immunotherapy in CCA patients.
- Subjects :
- Adult
Aged
Aged, 80 and over
B7-H1 Antigen antagonists & inhibitors
B7-H1 Antigen immunology
Bile Duct Neoplasms drug therapy
Bile Duct Neoplasms immunology
Bile Duct Neoplasms mortality
Bile Ducts, Intrahepatic immunology
Bile Ducts, Intrahepatic pathology
Cohort Studies
Female
Humans
Immunohistochemistry methods
Klatskin Tumor drug therapy
Klatskin Tumor immunology
Klatskin Tumor mortality
Male
Middle Aged
Neoplasm Staging
Staining and Labeling methods
Survival Analysis
Tissue Array Analysis
Antibodies immunology
B7-H1 Antigen metabolism
Bile Duct Neoplasms pathology
Klatskin Tumor pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1471-2407
- Volume :
- 19
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- BMC cancer
- Publication Type :
- Academic Journal
- Accession number :
- 30646854
- Full Text :
- https://doi.org/10.1186/s12885-018-5254-0