title: Associations among pretreatment tumor necrosis and the expression of HIF-1α and PD-L1 in advanced oral squamous cell carcinoma and the prognostic impact thereof.
abstract: OBJECTIVE
  The treatment strategies for advanced oral squamous cell carcinoma (OSCC), especially with necrotic changes, are not effective. The programmed death ligand 1 (PD-L1) immune escape may be one of the underlying sources of resistance. Furthermore, anti-PD-L1 directed immunotherapy may be another choice for adjuvant therapy. Therefore, the expression of PD-L1 in advanced OSCC with necrotic changes is very important.
  
  
  METHODS
  A total of 218 eligible patients with advanced stage (stage III/IV) OSCC and neck metastasis were enrolled. The presence of necrosis was reviewed by pretreatment magnetic resonance imaging. Paired paraffin-embedded primary tumor and metastatic lymph nodes (LN) sections were stained with antibodies against hypoxia-inducible factor-1α (HIF-1α) and PD-L1. Moderate-to strong HIF-1α nuclear staining in >10% and cell surface PD-L1 expression in >5% of OSCC cells were recorded as a positive result.
  
  
  RESULTS
  For advanced OSCC with necrotic changes, there was substantial agreement in primary tumor (kappa value 0.54) and almost perfect agreement in metastatic LN (kappa value 0.86) between HIF-1α and PD-L1 expression. The patients with both necrosis and positive PD-L1 expression in OSCC surrounding necrosis had worse disease control and survival outcomes. After multivariate analysis, metastatic LN necrosis and positive PD-L1 expression were found to be significant independent adverse factors.
  
  
  CONCLUSIONS
  Advanced OSCC patients with both necrosis and positive PD-L1 expression in OSCC surrounding necrosis had worse outcome. The aggressive behavior of advanced OSCC could be partially related to PD-L1 immune escape. These patients may be good candidates for anti-PD-L1 immunotherapy.
authors.affiliation: Department of Otolaryngology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 10002, Taiwan; Graduate Institute of Pathology, National Taiwan University College of Medicine, Taipei 10002, Taiwan.
authors.forename: Tseng-Cheng
authors.initials: TC
authors.lastname: Chen
authors.affiliation: Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 10002, Taiwan; Graduate Institute of Pathology, National Taiwan University College of Medicine, Taipei 10002, Taiwan.
authors.forename: Chen-Tu
authors.initials: CT
authors.lastname: Wu
authors.affiliation: Department of Otolaryngology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 10002, Taiwan; Graduate Institute of Pathology, National Taiwan University College of Medicine, Taipei 10002, Taiwan.
authors.forename: Cheng-Ping
authors.initials: CP
authors.lastname: Wang
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Wan-Lun
authors.initials: WL
authors.lastname: Hsu
authors.affiliation: Department of Otolaryngology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 10002, Taiwan.
authors.forename: Tsung-Lin
authors.initials: TL
authors.lastname: Yang
authors.affiliation: Department of Otolaryngology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 10002, Taiwan.
authors.forename: Pei-Jen
authors.initials: PJ
authors.lastname: Lou
authors.affiliation: Department of Otolaryngology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 10002, Taiwan.
authors.forename: Jenq-Yuh
authors.initials: JY
authors.lastname: Ko
authors.affiliation: Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei 10002, Taiwan; Graduate Institute of Pathology, National Taiwan University College of Medicine, Taipei 10002, Taiwan. Electronic address: ntuhylc@gmail.com.
authors.forename: Yih-Leong
authors.initials: YL
authors.lastname: Chang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060890:B7-H1 Antigen / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology*; D009333:Neck; D009336:Necrosis; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit
keywords: Advanced stage; Disease-free survivals; HIF-1α; Magnetic resonance imaging; Metastatic lymph nodes; Oral cancer; Overall survival; PD-L1 immune escape; Squamous cell carcinoma; Tumor necrosis