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Eur J Cancer. 2013 Jun;49(9):2233-42. doi: 10.1016/j.ejca.2013.02.015. Epub 2013 Mar 13.

Clinical impact of programmed cell death ligand 1 expression in colorectal cancer.

Author information

1
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.
2
Department of Surgery, University Hospital of Basel, Switzerland; Institute for Surgical Research and Hospital Management ICFS, Department of Biomedicine, University of Basel, Switzerland.
3
Department of Surgery, University Hospital of Basel, Switzerland.
4
Institute of Pathology, University of Bern, Switzerland.
5
Institute of Pathology, University of Basel, Switzerland.
6
Department of Surgery, Ospedale Regionale di Lugano, Switzerland.
7
Department of Surgery, Kantonsspital Olten, Switzerland.
8
Institute for Surgical Research and Hospital Management ICFS, Department of Biomedicine, University of Basel, Switzerland.
9
Institute of Translational Pharmacology, National Council Research, Rome, Italy.

Abstract

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.

PMID:
23478000
DOI:
10.1016/j.ejca.2013.02.015
[Indexed for MEDLINE]
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