title: Programmed death ligand-1 expression in adrenocortical carcinoma: an exploratory biomarker study.
abstract: BACKGROUND
  Adrenocortical carcinoma (ACC) is a rare tumor in which prognostic factors are still not well established. Programmed Death Ligand-1 (PD-L1) expression in ACC and its association with clinico-pathological features and survival outcomes are unknown.
  
  
  METHODS
  Formalin-fixed paraffin-embedded (FFPE) specimens were obtained from 28 patients with ACC. PD-L1 expression was evaluated by immunohistochemistry (IHC) in both tumor cell membrane and tumor infiltrating mononuclear cells (TIMC). PD-L1 positivity on tumor cells was defined as ≥5% tumor cell membrane staining. TIMC were evaluated by IHC using a CD45 monoclonal antibody. For PD-L1 expression in TIMC, a combined score based on the extent of infiltrates and percentage of positive cells was developed. Any score greater that zero was considered PD-L1 positive. Baseline clinico-pathological characteristics and follow up data were retrospectively collected. Comparisons between PD-L1 expression and clinico-pathological features were evaluated using unpaired t-test and Fisher's exact test. Kaplan-Meier method and log-rank test were used to assess association between PD-L1 expression and 5-year overall survival (OS).
  
  
  RESULTS
  Among 28 patients with surgically treated ACC, 3 (10.7%) were considered PD-L1 positive on tumor cell membrane. On the other hand, PD-L1 expression in TIMC was performed in 27 specimens and PD-L1 positive staining was observed in 19 (70.4%) patients. PD-L1 positivity in either tumor cell membrane or TIMC was not significantly associated with higher stage at diagnosis, higher tumor grade, excessive hormone secretion, or OS.
  
  
  CONCLUSIONS
  PD-L1 expression can exist in ACC in both tumor cell membrane and TIMC with no relationship to clinico-pathologic parameters or survival.
authors.affiliation: Dana-Farber Cancer Institute, 450 Brookline Avenue (DANA 1230), Boston, MA 02215 USA ; Programa de Pós-Graduação em Medicina e Ciências da Saúde, Faculdade de Medicina, Pontifícia Universidade Católica do Rio Grande do Sul, Av. Ipiranga 6690, Porto Alegre, RS 90619-900 Brazil.
authors.forename: André P
authors.initials: AP
authors.lastname: Fay
authors.affiliation: Brigham and Women's Hospital, 75 Francis Street (Thorn Building 504A), Boston, MA 02215 USA ; Harvard Medical School, 25 Shattuck Street, Boston, MA 02115 USA.
authors.forename: Sabina
authors.initials: S
authors.lastname: Signoretti
authors.affiliation: Brigham and Women's Hospital, 75 Francis Street (Thorn Building 504A), Boston, MA 02215 USA.
authors.forename: Marcella
authors.initials: M
authors.lastname: Callea
authors.affiliation: Joslin Diabetes Center, One Joslin Place, Boston, MA 02215 USA.
authors.forename: Gabriela H
authors.initials: GH
authors.lastname: Telό
authors.affiliation: Dana-Farber Cancer Institute, 450 Brookline Avenue (DANA 1230), Boston, MA 02215 USA ; Brigham and Women's Hospital, 75 Francis Street (Thorn Building 504A), Boston, MA 02215 USA ; Harvard Medical School, 25 Shattuck Street, Boston, MA 02115 USA.
authors.forename: Rana R
authors.initials: RR
authors.lastname: McKay
authors.affiliation: Brigham and Women's Hospital, 75 Francis Street (Thorn Building 504A), Boston, MA 02215 USA.
authors.forename: Jiaxi
authors.initials: J
authors.lastname: Song
authors.affiliation: Brigham and Women's Hospital, 75 Francis Street (Thorn Building 504A), Boston, MA 02215 USA.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Carvo
authors.affiliation: Dana-Farber Cancer Institute, 450 Brookline Avenue (DANA 1230), Boston, MA 02215 USA.
authors.forename: Megan E
authors.initials: ME
authors.lastname: Lampron
authors.affiliation: Dana-Farber Cancer Institute, 450 Brookline Avenue (DANA 1230), Boston, MA 02215 USA.
authors.forename: Marina D
authors.initials: MD
authors.lastname: Kaymakcalan
authors.affiliation: Programa de Pós-Graduação em Medicina e Ciências da Saúde, Faculdade de Medicina, Pontifícia Universidade Católica do Rio Grande do Sul, Av. Ipiranga 6690, Porto Alegre, RS 90619-900 Brazil.
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Poli-de-Figueiredo
authors.affiliation: Dana-Farber Cancer Institute, 450 Brookline Avenue (DANA 1230), Boston, MA 02215 USA ; Brigham and Women's Hospital, 75 Francis Street (Thorn Building 504A), Boston, MA 02215 USA ; Harvard Medical School, 25 Shattuck Street, Boston, MA 02115 USA.
authors.forename: Joaquim
authors.initials: J
authors.lastname: Bellmunt
authors.affiliation: Dana-Farber Cancer Institute, 450 Brookline Avenue (DANA 1230), Boston, MA 02215 USA ; Harvard Medical School, 25 Shattuck Street, Boston, MA 02115 USA ; Center of Immuno-Oncology, 450 Brookline Avenue, Boston, MA 02215 USA.
authors.forename: F Stephen
authors.initials: FS
authors.lastname: Hodi
authors.affiliation: Dana-Farber Cancer Institute, 450 Brookline Avenue (DANA 1230), Boston, MA 02215 USA ; Harvard Medical School, 25 Shattuck Street, Boston, MA 02115 USA.
authors.forename: Gordon J
authors.initials: GJ
authors.lastname: Freeman
authors.affiliation: Dana-Farber Cancer Institute, 450 Brookline Avenue (DANA 1230), Boston, MA 02215 USA ; Brigham and Women's Hospital, 75 Francis Street (Thorn Building 504A), Boston, MA 02215 USA ; Harvard Medical School, 25 Shattuck Street, Boston, MA 02115 USA.
authors.forename: Aymen
authors.initials: A
authors.lastname: Elfiky
authors.affiliation: Dana-Farber Cancer Institute, 450 Brookline Avenue (DANA 1230), Boston, MA 02215 USA ; Brigham and Women's Hospital, 75 Francis Street (Thorn Building 504A), Boston, MA 02215 USA ; Harvard Medical School, 25 Shattuck Street, Boston, MA 02115 USA.
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
keywords: Adrenocortical carcinoma; Immunotherapy; PD-1 inhibitors; PD-L1