Programmed death ligand-1 expression in adrenocortical carcinoma: an exploratory biomarker study

Abstract

BackgroundAdrenocortical 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.MethodsFormalin-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).ResultsAmong 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.ConclusionsPD-L1 expression can exist in ACC in both tumor cell membrane and TIMC with no relationship to clinico-pathologic parameters or survival.Electronic supplementary materialThe online version of this article (doi:10.1186/s40425-015-0047-3) contains supplementary material, which is available to authorized users.

Developing treatment for adrenocortical carcinoma

“…Blocking the programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1) receptor in an attempt to direct a T-cell response to tumour tissue has been successful in renal cell carcinoma, melanoma and non-small cell lung carcinoma (Topalian et al 2012). Exploratory research on a small scale (nZ28) demonstrated ACC may express PD-L1 on the cell surface (Fay et al 2015). A phase I study with the PD-L1 inhibitor avelumab is currently recruiting and is open to ACC patients (NCT01772004).…”

Immunotherapy against endocrine malignancies: immune checkpoint inhibitors lead the way

“…Adrenocortical carcinoma is an aggressive disease, and the stage of the tumor at diagnosis is the factor with the greatest impact on prognosis (Kerkhofs et al 2015). Fay and coworkers investigated the expression of PD-L1 in adrenocortical carcinoma tissues (Fay et al 2015). …”

The challenge of developmental therapeutics for adrenocortical carcinoma

“…There was no correlation between PD-L1 expression and overall survival, higher tumor grade or stage at diagnosis. [131] The role of immune checkpoints in the pathophysiology of ACC and its possible therapeutic implication remains to be determined. Clinical trials evaluating this strategy will be soon recruiting patients (NCT02673333, NCT02720484 and NCT02720484).…”