The Role of PD-L1, Ki-67, P53 and Cyclin D1 in PitNETs: Diagnostic and Prognostic Implications. A Series of 74 Patients

Objective: The aim of our study was to assess the expression of Programmed death-ligand 1 (PD-L1) and proliferation biomarkers (Ki-67, cyclin D1 and P53) in Pituitary Neuroendocrine Tumors (PitNETs) depending on the transcription factor and adenoma subtype. Material and methods: The analysis was performed in seventy-four patients operated on in a single neurosurgical centre for pituitary tumor. Immunohistochemistry was performed for transcription factors and biomarkers: PD-L, Ki-67, P53 and cyclin D1 in tissue microarray format. Membranous expression of PD-L1 was scored as 0 (no expression) and ≥1%. Nuclear expression of Ki-67 was scored at <3% and ≥3%, expression of P53 and Cyclin D1 were scored at <10% and ≥10%. Results: The following tumors expressed PD-L1≥1%: gonadotroph - 21 (28.4%), corticotroph - 5 (6.7%), gonadotroph/lactotroph - 2 (2.7%), null cell adenoma - 3 (4.0%), multiple synchronous PitNET - 2 (2.7%); immature PIT-1 tumour – 1 (1.3%); mature PIT-1 tumor -1 (1.5%). KI≥3% was found in the following types of PITNETs: gonadotroph – 3 (4.0%), corticotroph - 2 (2.7%), lactotroph – 1 (1.3%), multiple synchronous PitNET – 1 (1.3%), immature PIT-1 tumor -1 (1.3%), mature PIT-1 tumor -1 (1.3%). Of the four factors, PD-L1 increased the odds of invasiveness the most (adjusted OR = 2.35; 95% CI: 0.56–9.90). Patients with K≥3% were statistically significantly younger (p=0.03). All tumors (100%) with a combination of Cyclin D1≥10% & P53<10% were invasive on the Hardy scale. Conclusions: PD-L1 expression was present in some types of PitNETs, which may play a role in immunotherapy. CyclinD1 D>10% may affect the invasiveness of PitNETs. Further studies are needed in a larger group of patients to determine the importance of this factor, as well as studies on the role of cyclin D1 in PitNETs.