Journal article
Clinical impact of programmed cell death ligand 1 expression in colorectal cancer.
- Droeser RA Department of Surgery, University Hospital of Basel, Switzerland; Institute for Surgical Research and Hospital Management ICFS, Department of Biomedicine, University of Basel, Switzerland. Electronic address: rdroeser@uhbs.ch.
- Hirt C Department of Surgery, University Hospital of Basel, Switzerland; Institute for Surgical Research and Hospital Management ICFS, Department of Biomedicine, University of Basel, Switzerland.
- Viehl CT Department of Surgery, University Hospital of Basel, Switzerland.
- Frey DM Department of Surgery, University Hospital of Basel, Switzerland.
- Nebiker C Department of Surgery, University Hospital of Basel, Switzerland; Institute for Surgical Research and Hospital Management ICFS, Department of Biomedicine, University of Basel, Switzerland.
- Huber X Department of Surgery, University Hospital of Basel, Switzerland.
- Zlobec I Institute of Pathology, University of Bern, Switzerland.
- Eppenberger-Castori S Institute of Pathology, University of Basel, Switzerland.
- Tzankov A Institute of Pathology, University of Basel, Switzerland.
- Rosso R Department of Surgery, Ospedale Regionale di Lugano, Switzerland.
- Zuber M Department of Surgery, Kantonsspital Olten, Switzerland.
- Muraro MG Institute for Surgical Research and Hospital Management ICFS, Department of Biomedicine, University of Basel, Switzerland.
- Amicarella F Institute for Surgical Research and Hospital Management ICFS, Department of Biomedicine, University of Basel, Switzerland.
- Cremonesi E Institute for Surgical Research and Hospital Management ICFS, Department of Biomedicine, University of Basel, Switzerland.
- Heberer M Institute for Surgical Research and Hospital Management ICFS, Department of Biomedicine, University of Basel, Switzerland.
- Iezzi G Institute for Surgical Research and Hospital Management ICFS, Department of Biomedicine, University of Basel, Switzerland.
- Lugli A Institute of Pathology, University of Bern, Switzerland.
- Terracciano L Institute of Pathology, University of Basel, Switzerland.
- Sconocchia G Institute of Translational Pharmacology, National Council Research, Rome, Italy.
- Oertli D Department of Surgery, University Hospital of Basel, Switzerland.
- Spagnoli GC Institute for Surgical Research and Hospital Management ICFS, Department of Biomedicine, University of Basel, Switzerland.
- Tornillo L Institute of Pathology, University of Basel, Switzerland.
- 2013-03-13
Published in:
- European journal of cancer (Oxford, England : 1990). - 2013
Adult
Aged
Aged, 80 and over
Antigens, Neoplasm
B7-H1 Antigen
Biomarkers, Tumor
CD8-Positive T-Lymphocytes
Colonic Neoplasms
DNA Mismatch Repair
Female
Humans
Kaplan-Meier Estimate
Lymphocytes, Tumor-Infiltrating
Male
Middle Aged
Prognosis
Rectal Neoplasms
Tissue Array Analysis
English
BACKGROUND
Programmed cell death 1 (PD-1) receptor triggering by PD ligand 1 (PD-L1) inhibits T cell activation. PD-L1 expression was detected in different malignancies and associated with poor prognosis. Therapeutic antibodies inhibiting PD-1/PD-L1 interaction have been developed.
MATERIALS AND METHODS
A tissue microarray (n=1491) including healthy colon mucosa and clinically annotated colorectal cancer (CRC) specimens was stained with two PD-L1 specific antibody preparations. Surgically excised CRC specimens were enzymatically digested and analysed for cluster of differentiation 8 (CD8) and PD-1 expression.
RESULTS
Strong PD-L1 expression was observed in 37% of mismatch repair (MMR)-proficient and in 29% of MMR-deficient CRC. In MMR-proficient CRC strong PD-L1 expression correlated with infiltration by CD8(+) lymphocytes (P = 0.0001) which did not express PD-1. In univariate analysis, strong PD-L1 expression in MMR-proficient CRC was significantly associated with early T stage, absence of lymph node metastases, lower tumour grade, absence of vascular invasion and significantly improved survival in training (P = 0.0001) and validation (P = 0.03) sets. A similar trend (P = 0.052) was also detectable in multivariate analysis including age, sex, T stage, N stage, tumour grade, vascular invasion, invasive margin and MMR status. Interestingly, programmed death receptor ligand 1 (PDL-1) and interferon (IFN)-γ gene expression, as detected by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) in fresh frozen CRC specimens (n = 42) were found to be significantly associated (r = 0.33, P = 0.03).
CONCLUSION
PD-L1 expression is paradoxically associated with improved survival in MMR-proficient CRC.
Programmed cell death 1 (PD-1) receptor triggering by PD ligand 1 (PD-L1) inhibits T cell activation. PD-L1 expression was detected in different malignancies and associated with poor prognosis. Therapeutic antibodies inhibiting PD-1/PD-L1 interaction have been developed.
MATERIALS AND METHODS
A tissue microarray (n=1491) including healthy colon mucosa and clinically annotated colorectal cancer (CRC) specimens was stained with two PD-L1 specific antibody preparations. Surgically excised CRC specimens were enzymatically digested and analysed for cluster of differentiation 8 (CD8) and PD-1 expression.
RESULTS
Strong PD-L1 expression was observed in 37% of mismatch repair (MMR)-proficient and in 29% of MMR-deficient CRC. In MMR-proficient CRC strong PD-L1 expression correlated with infiltration by CD8(+) lymphocytes (P = 0.0001) which did not express PD-1. In univariate analysis, strong PD-L1 expression in MMR-proficient CRC was significantly associated with early T stage, absence of lymph node metastases, lower tumour grade, absence of vascular invasion and significantly improved survival in training (P = 0.0001) and validation (P = 0.03) sets. A similar trend (P = 0.052) was also detectable in multivariate analysis including age, sex, T stage, N stage, tumour grade, vascular invasion, invasive margin and MMR status. Interestingly, programmed death receptor ligand 1 (PDL-1) and interferon (IFN)-γ gene expression, as detected by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) in fresh frozen CRC specimens (n = 42) were found to be significantly associated (r = 0.33, P = 0.03).
CONCLUSION
PD-L1 expression is paradoxically associated with improved survival in MMR-proficient CRC.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1016/j.ejca.2013.02.015
- PMID 23478000
- Persistent URL
- https://sonar.ch/global/documents/1338
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