title: Characterisation of PD-L1-positive subsets of microsatellite-unstable colorectal cancers.
abstract: The aim of this study was to reveal the clinicopathological and molecular characteristics of microsatellite instability-high (MSI-H) colorectal cancers (CRCs) showing programmed death ligand-1 (PD-L1) positivity, which are good candidates for anti-PD-1/PD-L1 immunotherapy.
  
  
  
  The PD-L1 expression status of 208 MSI-H CRCs was retrospectively analysed using immunohistochemistry. PD-L1 positivity in tumour cells (PD-L1+(T)) and PD-L1 positivity in immune cells (PD-L1+(I)) were separately evaluated.
  
  
  
  Programmed death ligand-1 positivity in tumour cells and PD-L1+(I) were observed in 26 (12.5%) and 62 (29.8%) MSI-H CRCs, respectively, and occasionally overlapped (n=12; 5.8%). Programmed death ligand-1 positivity tumours in MSI-H CRCs were significantly associated with older age, female sex, non-mucinous-type poor differentiation, infiltrating growth, tumour budding, advanced stage, CpG island methylator phenotype-high, MLH1 promoter methylation, and BRAF V600E mutations. However, PD-L1+(I) MSI-H CRCs were characterised by high-density tumour-infiltrating immune cells, including T cells and macrophages, and intense peritumoural lymphoid reactions. In patients with stage IV MSI-H CRCs who had undergone metastatectomy (n=4), the PD-L1 status of primary tumours was maintained in corresponding distant metastatic lesions.
  
  
  
  In MSI-H CRCs, PD-L1+(T) and PD-L1+(I) are linked to a sporadic hypermethylated subtype and an immune cell-rich subtype, respectively. Potential differential therapeutic implications of PD-L1+(T) and PD-L1+(I) in CRCs should be further investigated.
authors.affiliation: Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, 103 Daehak-ro, Seoul 03080, Republic of Korea.
authors.forename: Jung Ho
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, 103 Daehak-ro, Seoul 03080, Republic of Korea.
authors.forename: Hye Eun
authors.initials: HE
authors.lastname: Park
authors.affiliation: Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Seoul 03080, Republic of Korea.
authors.forename: Nam-Yun
authors.initials: NY
authors.lastname: Cho
authors.affiliation: Department of Pathology, Seoul National University Bundang Hospital, 82 Gumi-ro 173-gil, Bundang-gu, Seongnam-si 13620, Republic of Korea.
authors.forename: Hye Seung
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, 103 Daehak-ro, Seoul 03080, Republic of Korea.|Laboratory of Epigenetics, Cancer Research Institute, Seoul National University College of Medicine, 103 Daehak-ro, Seoul 03080, Republic of Korea.
authors.forename: Gyeong Hoon
authors.initials: GH
authors.lastname: Kang
mesh_terms: D000367:Age Factors; D060890:B7-H1 Antigen / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D000070957:MutL Protein Homolog 1 / Q000235:genetics; D009154:Mutation; D009367:Neoplasm Staging; D011401:Promoter Regions, Genetic / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D012189:Retrospective Studies; D012737:Sex Factors
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; C501486:MLH1 protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D000070957:MutL Protein Homolog 1