Introduction: Pituitary adenomas, second most common brain tumors, are mostly well controlled after surgery. However, some pituitary tumors present an aggressive evolution and are resistant to standard management. Immunotherapy with inhibitors of T-cell checkpoints have shown durable efficacy in a variety of malignancies. Moreover, immunotherapy has been associated with treatment-related hypophysitis, suggesting that pituitary could be a target of these treatments. Recently, it has been shown that adenomas frequently express programmed death ligand 1 (PD-L1) transcript and/or protein. However, association between expression and clinical characteristics has been poorly studied. The aim of this study was to assess the PD-L1 expression in each subtypes of pituitary adenomas.
Methods: The subjects enrolled in this study were patients who had been treated in the Academic Hospital of Angers (France) for a pituitary adenoma between 2012 and 2018. We performed immunohistochemical analysis on tissue of the surgical specimens using the validated PD-L1 antibody clone for therapeutic issue [Clone 22C3 pharmDx, Agilent-Dako]. Staining was performed using a Bond III from Leica. PDL-1 positivity was defined by the presence of partial or complete linear membrane staining on tumoral cell, with different cutoffs: 5%, 25%, and 50%. Mitotic count, Ki-67 and p53 expression were also assessed. The association between PD-L1 expression and clinicopathologic parameters and imaging features was analyzed.
Results: Among the 149 patients retrospectively included in this study, 134 pituitary tumors were analyzed, consisting in 83 (63%) nonfunctioning adenomas, 19 (14%) ACTH-secreting adenomas, 18 (13%) GH-secreting adenomas, 9 (7%) PRL-secreting adenomas and 4 (3%) PRL-GH secreting adenomas. Eleven of them were PD-L1 positive (8.3%), including 3 diffuse stainings (>25% of cells) and 8 weak stainings (<5% of cells). The positive PD-L1 immunostaining was more frequent in non-invasive tumors (80%) than in invasive pituitary adenomas (20% of PD-L1 positive) (P=0.0014). All tumors with Ki-67 ≥ 3% were PD-L1 negative and recurrent tumors didnt exhibit a PD-L1 expression. Moreover, PD-L1 expression was not different between functioning and non-functioning adenomas (P=0.57).
Conclusion: Our results showed that pituitary adenomas exhibited weak PD-L1 expression as compared to the literature, with another PD-L1 antibody. We found a significantly lower expression in proliferative and invasive adenomas. PD-L1 expression seems to be associated with non-aggressive behaviors in pituitary adenomas and may be a predictive marker for favorable outcomes. This study didnt raise the possibility of considering checkpoint blockade immunotherapy in cases of refractory adenomas.
18 - 21 May 2019
European Society of Endocrinology