+1 Recommend
1 collections
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Association of programmed death ligand 1 expression with prognosis among patients with ten uncommon advanced cancers


      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.



          PD-L1 expression and high levels of microsatellite instability (MSI-H) may predict response to checkpoint inhibitors, but their prevalence and prognostic value are unknown in many cancers.


          We retrospectively evaluated PD-L1 combined positive score (CPS) and MSI-H and their association with clinical outcomes among patients with ten advanced uncommon cancers.


          398 of 426 patients (93%) had a valid PD-L1 result; most (242; 61%) had CPS ≥1. Prevalence of MSI-H tumors was 8/360. Median overall survival was shorter among patients with PD-L1 CPS ≥1 tumors after first-line treatment (23.0 vs 39.7 months, p = 0.014).


          PD-L1 was commonly expressed in solid tumors, and CPS ≥1 was associated with shorter overall survival. Prevalence of MSI-H was low.

          Lay abstract

          Certain biologic characteristics of tumors (or biomarkers) may be used to assess the likely course of a patient’s disease (i.e., their prognosis) and/or how they may respond to treatment. We evaluated whether the presence of the protein PD-L1 and high levels of microsatellite instability were associated with overall survival among patients with ten uncommon advanced cancers. PD-L1 was commonly expressed in solid tumors and its presence may be associated with shorter overall survival. Prevalence of high microsatellite instability was low.

          Most cited references20

          • Record: found
          • Abstract: not found
          • Article: not found

          Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Cervical Cancer: Results From the Phase II KEYNOTE-158 Study

            • Record: found
            • Abstract: found
            • Article: not found

            Programmed death ligand-1 expression in non-small cell lung cancer.

            Recent strategies targeting the interaction of the programmed cell death ligand-1 (PD-L1, B7-H1, CD274) with its receptor, PD-1, resulted in promising activity in early phase clinical trials. In this study, we used various antibodies and in situ mRNA hybridization to measure PD-L1 in non-small cell lung cancer (NSCLC) using a quantitative fluorescence (QIF) approach to determine the frequency of expression and prognostic value in two independent populations. A control tissue microarray (TMA) was constructed using PD-L1-transfected cells, normal human placenta and known PD-L1-positive NSCLC cases. Only one of four antibodies against PD-L1 (5H1) validated for specificity on this TMA. In situ PD-L1 mRNA using the RNAscope method was similarly validated. Two cohorts of NSCLC cases in TMAs including 340 cases from hospitals in Greece and 204 cases from Yale University were assessed. Tumors showed PD-L1 protein expression in 36% (Greek) and 25% (Yale) of the cases. PD-L1 expression was significantly associated with tumor-infiltrating lymphocytes in both cohorts. Patients with PD-L1 (both protein and mRNA) expression above the detection threshold showed statistically significant better outcome in both series (log-rank P=0.036 and P=0.027). Multivariate analysis showed that PD-L1 expression was significantly associated with better outcome independent of histology. Measurement of PD-L1 requires specific conditions and some commercial antibodies show lack of specificity. Expression of PD-L1 protein or mRNA is associated with better outcome. Further studies are required to determine the value of this marker in prognosis and prediction of response to treatments targeting this pathway.
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              A molecular portrait of microsatellite instability across multiple cancers

              Microsatellite instability (MSI) refers to the hypermutability of short repetitive sequences in the genome caused by impaired DNA mismatch repair. Although MSI has been studied for decades, large amounts of sequencing data now available allows us to examine the molecular fingerprints of MSI in greater detail. Here, we analyse ∼8,000 exomes and ∼1,000 whole genomes of cancer patients across 23 cancer types. Our analysis reveals that the frequency of MSI events is highly variable within and across tumour types. We also identify genes in DNA repair and oncogenic pathways recurrently subject to MSI and uncover non-coding loci that frequently display MSI. Finally, we propose a highly accurate exome-based predictive model for the MSI phenotype. These results advance our understanding of the genomic drivers and consequences of MSI, and our comprehensive catalogue of tumour-type-specific MSI loci will enable panel-based MSI testing to identify patients who are likely to benefit from immunotherapy.

                Author and article information

                Future Sci OA
                Future Sci OA
                Future Science OA
                Future Science Ltd (London, UK )
                19 August 2020
                September 2020
                19 August 2020
                : 6
                : 8
                : FSO616
                [1 ]Institute of Pathology, Aarhus University Hospital, Aarhus DK-8200, Denmark
                [2 ]Department of Oncology, Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark
                [3 ]Department of Otorhinolaryngology, Head & Neck Surgery & Audiology, Copenhagen University Hospital, Copenhagen, Denmark
                [4 ]Department of Otorhinolaryngology & Maxillofacial Surgery, Zealand University Hospital, Køge, Denmark
                [5 ]Busch-Sørensen Consulting, Virum, Denmark
                [6 ]Merck & Co., Inc., Kenilworth, NJ, USA
                Author notes
                [* ]Author for correspondence: Tel.: +45 2281 6894; torbstei@ 123456rm.dk

                Dedicated to the memory of the late Simon Andreasen

                © 2020 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA

                This work is licensed under the Creative Commons Attribution 4.0 License

                : 09 April 2020
                : 22 June 2020
                : 19 August 2020
                Page count
                Pages: 11
                Research Article

                anal carcinoma,biliary adenocarcinoma,cervical carcinoma,endometrial carcinoma,mesothelioma,neuroendocrine tumors,salivary gland carcinoma,small-cell lung carcinoma,thyroid carcinoma,vulvar carcinoma


                Comment on this article