PD-L1 expression in PitNETs: Correlations with the 2022 WHO classification

Introduction: and research question: Prognostic factors to predict the behavior of pituitary neuroendocrine tumors (PitNET) are scarce. PD-L1 expression was associated with prognosis in other neuroendocrine neoplasms and we analyzed PD-L1 expression in PitNET, according to the 2022 WHO classification. Material and methods: A retrospective analysis was performed. Immunohistochemistry was used to define PD-L1 expression, which was quantified as TPS (tumor proportion score). The primary outcome was to assess the correlation between PD-L1 expression and transcription factors (TF), namely T-pit, Pit-1, SF-1 and GATA-3. As secondary outcomes, we evaluated the association between PD-L1 expression and proliferation indexes. Results: Eighty-eight patients were included. The largest group belonged to the SF-1-lineage (48%), followed by tumors of the Pit-1 lineage (32%) and T-pit lineage (17%). PD-L1 expression was associated with Pit-1 expression (p < 0.001) and with the somatotroph, lactotroph and mammosomatotroph subgroups. A TPS ⩾35% showed a 100% sensitivity for the mammosomatotroph subtype, while the optimal cut-off point was 20% for somatotroph and 15% for lactotroph tumors. PD-L1 expression was negatively associated with SF-1 and GATA3 expression(p < 0.001), with an optimal cut-point ≤5%. No association was found between PD-L1 expression and immunohistochemical proliferative factors but PD-L1 expression was associated with female sex and a younger age at diagnosis. Conclusion: PD-L1 expression was associated with PIT-1 lineage, while it was downregulated in SF-1-lineage tumors. No correlation was found with proliferative factors. The role of PD-L1 expression in determining the biological behavior of PitNET remains debated and larger studies are necessary to further confirm these findings.