title: Programmed Death - Ligand 1 Expression Distinguishes Invasive Encapsulated Follicular Variant of Papillary Thyroid Carcinoma from Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features.
abstract: BACKGROUND
  The noninvasive Encapsulated follicular variant of papillary thyroid cancer (EFVPTC) has been reclassified as Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) without a significant risk for malignant behavior. However the evaluation remains a challenge for clinicians. We sought to determine whether programmed death-ligand 1 (PD-L1) expression may serve as a biomarker to predict invasiveness of EFVPTC and assist to distinguish these neoplasms from NIFTP.
  
  
  METHODS
  Immunohistochemical staining of PD-L1 expression was performed in sections of 174 Formalin-fixed paraffin-embedded (FFPE) tissue blocks from surgery removed thyroid nodules.
  
  
  RESULTS
  Cytoplasmic PD-L1 expression was significantly increased in invasive EFVPTC (4.76±1.49) as compared to NIFTP (3.06±2.16, p<0.001). Increased cytoplasmic PD-L1 expression was associated with invasiveness in EFVPTC (p<0.001); PD-L1 positive EFVPTC cases were at 3.16 folds higher risk in developing invasion than the PD-L1 negative cases. No significant difference in cytoplasmic PD-L1 expression was observed between NIFTP and benign nodules.
  
  
  CONCLUSIONS
  PD-L1 expression may serve as a useful biomarker in predicting invasiveness of EFVPTC and distinguishing NIFTP from invasive EFVPTC. To our knowledge this is the first report suggesting the application of a protein biomarker to confirm NIFTP as benign indolent neoplasms.
authors.affiliation: Alex and Simona Shnaider Research Laboratory in Molecular Oncology, Mount Sinai Hospital, Toronto, ON, Canada.
authors.forename: Guodong
authors.initials: G
authors.lastname: Fu
authors.affiliation: Alex and Simona Shnaider Research Laboratory in Molecular Oncology, Mount Sinai Hospital, Toronto, ON, Canada.
authors.forename: Olena
authors.initials: O
authors.lastname: Polyakova
authors.affiliation: Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada; Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Christina
authors.initials: C
authors.lastname: MacMillan
authors.affiliation: Alex and Simona Shnaider Research Laboratory in Molecular Oncology, Mount Sinai Hospital, Toronto, ON, Canada; Joseph and Mildred Sonshine Family Centre for Head and Neck Diseases, Department of Otolaryngology-Head and Neck Surgery Program, Mount Sinai Hospital, Toronto, Ontario, Canada; Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada; Department of Otolaryngology-Head and Neck Surgery, Mount Sinai Hospital, Toronto, Ontario, Canada; Department of Otolaryngology-Head and Neck Surgery, University of Toronto, Toronto, Ontario, Canada; Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. Electronic address: Ranju.Ralhan@sinaihealthsystem.ca.
authors.forename: Ranju
authors.initials: R
authors.lastname: Ralhan
authors.affiliation: Alex and Simona Shnaider Research Laboratory in Molecular Oncology, Mount Sinai Hospital, Toronto, ON, Canada; Joseph and Mildred Sonshine Family Centre for Head and Neck Diseases, Department of Otolaryngology-Head and Neck Surgery Program, Mount Sinai Hospital, Toronto, Ontario, Canada; Department of Otolaryngology-Head and Neck Surgery, Mount Sinai Hospital, Toronto, Ontario, Canada; Department of Otolaryngology-Head and Neck Surgery, University of Toronto, Toronto, Ontario, Canada; Department of Medicine, Endocrine Division, Mount Sinai Hospital, Toronto, Ontario, Canada; University of Toronto Medical School, Toronto, Ontario, Canada. Electronic address: Paul.Walfish@sinaihealthsystem.ca.
authors.forename: Paul G
authors.initials: PG
authors.lastname: Walfish
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002291:Carcinoma, Papillary / Q000378:metabolism / Q000473:pathology*; D018265:Carcinoma, Papillary, Follicular / Q000378:metabolism / Q000473:pathology*; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism*; D012189:Retrospective Studies; D013964:Thyroid Neoplasms / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult
chemical_list: C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
keywords: Follicular variant; Invasion; NIFTP; PD-L1; PTC; Protein biomarker; Thyroid cancer