title: Do programmed death 1 (PD-1) and its ligand (PD-L1) play a role in patients with non-clear cell renal cell carcinoma?
abstract: Clinical trials targeting programmed death 1 (PD-1) and its ligand PD-L1 (PD-L1) for metastatic renal cell cancer (RCC) are ongoing. The aim of this study is to validate their roles as prognostic markers in non-clear cell (non-cc) RCC. Sixty-four non-cc RCC tissue specimens were collected from patients undergoing renal tumor surgery. Expressions of biomarkers were assessed using immunohistochemistry and compared with clinical characteristics. Survival analyses were performed with a median follow-up of 77.5 (range: 0-176) months. No significant correlations were found for PD-1(+) tumor-infiltrating mononuclear cells (TIMC) or PD-L1(+) expression and clinical attributes in patients with non-cc RCC. Kaplan-Meier analysis revealed no differences in 5- and 10-year cancer-specific survival (CSS) for PD-1(-) TIMC compared to PD-1(+) TIMC (71.4 and 63 % versus 72.2 and 61.9 %; p = 0.88). Intratumoral expression of PD-L1 did not appear to influence the 5- and 10-year CSS significantly, even though a trend was identified (68 and 53.6 % versus 80.1 and 75.7 %; p = 0.08). In multivariate analysis, neither PD-1(+) TIMC nor intratumoral PD-L1(+) expression proved to be independent predictors of CSS (p = 0.99 and p = 0.68, respectively). Our study demonstrates that PD-1(+) TIMC and intratumoral PD-L1(+) expression did not significantly impact tumor aggressiveness or clinical outcome in non-ccRCC specimens. Due to rare incidence of non-cc RCC in particular according to PD-L1 expression, further analyzes are warranted.
authors.affiliation: Institute of Pathology, Hannover Medical School, Carl-Neuberg Street 1, 30625, Hannover, Germany.
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Abbas
authors.affiliation: Department of Urology and Urologic Oncology, Hannover Medical School, Carl-Neuberg Street 1, 30625, Hannover, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Steffens
authors.affiliation: Department of Urology and Urologic Oncology, Hannover Medical School, Carl-Neuberg Street 1, 30625, Hannover, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Bellut
authors.affiliation: Institute of Pathology, University Hospital of Cologne, Cologne, Germany.
authors.forename: Jan U
authors.initials: JU
authors.lastname: Becker
authors.affiliation: Institute of Bimetrics, Hannover Medical School, Carl-Neuberg Street 1, 30625, Hannover, Germany.
authors.forename: Anika
authors.initials: A
authors.lastname: Großhennig
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Carl-Neuberg Street 1, 30625, Hannover, Germany.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Eggers
authors.affiliation: Tumor Center, Hannover Medical School, Carl-Neuberg Street 1, 30625, Hannover, Germany.
authors.forename: Gerd
authors.initials: G
authors.lastname: Wegener
authors.affiliation: Department of Urology and Urologic Oncology, Hannover Medical School, Carl-Neuberg Street 1, 30625, Hannover, Germany.
authors.forename: Markus A
authors.initials: MA
authors.lastname: Kuczyk
authors.affiliation: Institute of Pathology, Hannover Medical School, Carl-Neuberg Street 1, 30625, Hannover, Germany.
authors.forename: Hans H
authors.initials: HH
authors.lastname: Kreipe
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Carl-Neuberg Street 1, 30625, Hannover, Germany.
authors.forename: Viktor
authors.initials: V
authors.lastname: Grünwald
authors.affiliation: Department of Urology, University of Muenster, Muenster, Germany.
authors.forename: Andres J
authors.initials: AJ
authors.lastname: Schrader
authors.affiliation: Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Carl-Neuberg Street 1, 30625, Hannover, Germany. Ivanyi.Philipp@mh-hannover.de.
authors.forename: Philipp
authors.initials: P
authors.lastname: Ivanyi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060890:B7-H1 Antigen / Q000096:biosynthesis*; D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D061026:Programmed Cell Death 1 Receptor / Q000096:biosynthesis*
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
keywords: Non-clear cell renal cell carcinoma; PD-1; PD-L1; Renal cell carcinoma; Survival