title: Diagnostic and prognostic utility of PD-1 in B cell lymphomas.
abstract: OBJECTIVE
  Programmed death-1 (PD-1) is expressed by germinal center-associated helper T-cells and acts as a negative regulator of the immune system. PD-1 is encountered on tumor cells of angioimmunoblastic T-cell lymphoma and is a postulated diagnostic marker in chronic lymphocytic leukemia (CLL/SLL). Recent data suggest prognostic importance of PD-1 in follicular lymphoma (FL). We assessed the diagnostic potential and the prognostic importance of PD-1 in B-cell lymphomas.
  
  
  METHODS
  Distribution of PD-1+ lymphocytes in B-cell lymphomas was studied on 403 cases. Correlation with known biologic and clinical key data was performed. Prognostic cut-off scores were determined by receiver operating curve analysis.
  
  
  RESULTS
  PD-1+ tumor-infiltrating lymphocytes were numerous in extranodal marginal zone lymphomas and FL. Their amount decreased from FL grade 1 to grade 3 and to FL with transformation to diffuse large B-cell lymphoma. An increased amount of PD-1 tumor-infiltrating lymphocytes above the prognostic cut-off score (> 2.8%) was a positive prognostic factor of disease-specific survival (DSS) in FL-patients. Five percent of the studied 66 CLL/SLL cases showed unequivocal PD-1 positivity of neoplastic cells.
  
  
  CONCLUSIONS
  Increased number of PD-1+ tumor-infiltrating lymphocytes is associated with significantly improved DSS in FL and may be useful to predict its heterogeneous clinical behavior. PD-1 has probably limited diagnostic value for primary histopathological CLL/SLL diagnostics.
authors.affiliation: Institute of Pathology, University Hospital, Schönbeinstrasse 40, Basel, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Muenst
authors.forename: S
authors.initials: S
authors.lastname: Hoeller
authors.forename: N
authors.initials: N
authors.lastname: Willi
authors.forename: S
authors.initials: S
authors.lastname: Dirnhofera
authors.forename: A
authors.initials: A
authors.lastname: Tzankov
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor
chemical_list: D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D014408:Biomarkers, Tumor; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor