title: Clinicopathologic Analysis of PD-L1 and PD-L2 Expression in  Renal Cell Carcinoma: Association with Oncogenic Proteins  Status.
abstract: BACKGROUND
  Immune checkpoint blockade therapy targeting programmed death (PD)-1 or PD-ligand 1 (L1) has shown promising results in renal cell carcinoma (RCC);however, the prognostic implications and clinicopathological features of PD-L1 and PD-L2 expression in RCC remain unclear.
  
  
  METHODS
  PD-L1 and PD-L2 expression was immunohistochemically evaluated in 425 resected RCCs of variable histologic subtypes and analyzed according to the clinicopathological status and oncogenic proteins status.
  
  
  RESULTS
  PD-L1 expression was observed in 9.4 % with no difference between histologic subtypes, but PD-L2 was observed in 49.6 % with highest frequency in papillary RCC (PRCC) (P<0.001). In clear cell RCC (CCRCC), PD-L1 expression was associated with adverse features,including higher nuclear grade, necrosis, sarcomatoid transformation, c-MET expression (all, P<0.001) and VEGF expression (P = 0.002), whereas PD-L2 expression was related with c-MET and VEGF expression (P = 0.008 and P<0.001). In PRCC, positive correlations between PD-L1 and EGFR expression (P = 0.007) or between PDL2 and VEGF expression (P<0.001) were observed. In CCRCC, PD-L1 and PD-L2 positivity were significantly associated with shorter progression-free survival (P<0.001; P = 0.033) and cancer-specific survival (P<0.001; P = 0.010), but not in PRCC.
  
  
  CONCLUSIONS
  PD-L1 and PD-L2 expression predict poor prognosis in CCRCC. Thus, PD-1/PD-L pathway-targeted immunotherapy may be useful for treatment of patients with CCRCC.
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Shin
authors.forename: Yoon Kyung
authors.initials: YK
authors.lastname: Jeon
authors.forename: Pil-Jong
authors.initials: PJ
authors.lastname: Kim
authors.forename: Yong Mee
authors.initials: YM
authors.lastname: Cho
authors.forename: Jaemoon
authors.initials: J
authors.lastname: Koh
authors.forename: Doo Hyun
authors.initials: DH
authors.lastname: Chung
authors.forename: Heounjeong
authors.initials: H
authors.lastname: Go
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060890:B7-H1 Antigen / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002291:Carcinoma, Papillary / Q000378:metabolism / Q000556:secondary*; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000556:secondary*; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D011379:Prognosis; D061027:Programmed Cell Death 1 Ligand 2 Protein / Q000378:metabolism*; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D055815:Young Adult
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; C556977:PDCD1LG2 protein, human; D061027:Programmed Cell Death 1 Ligand 2 Protein; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C512478:EGFR protein, human; D066246:ErbB Receptors; D019859:Proto-Oncogene Proteins c-met