Beata Biesaga

Pituitary neuroendocrine tumors (PitNETs) are usually benign intracranial neoplasms that may exhibit invasion of the cavernous sinus, complicating surgery and increasing the risk of recurrence. This study aimed to investigate membranous E-cadherin (mE-cad) expression across PitNET subtypes and transcription factor (TF) lineages, including Pit-1 (pituitary-specific positive transcription factor 1), SF-1 (Steroidogenic Factor 1), and TPIT (T-box pituitary transcription factor), and its association with tumor invasiveness in sixty-nine patients. mE-cad expression was evaluated as the percentage of positive cells (0%, 1–10%, >10%) and by immunoreactive score (IRS). Staining intensity was scored as: 0, no staining; 1, weak; 2, moderate; 3, strong. The proportion of positive cells was scored as: 0, none; 1, 80%. Mean mE-cad expression was 5.2% in gonadotroph, 3.2% in corticotroph, 0.5% in lactotroph, and 17.5% in plurihormonal PitNETs. By TF lineage, the mean expression was 5.3% for Pit-1, 3.2% for TPIT, and 5.1% for SF-1. Low mE-cad expression (IRS 1–2) was associated with higher odds of cavernous sinus invasion compared with IRS 3–6 (adjusted OR = 6.0, 95% CI 1.08–33.4, p = 0.04), independent of tumor volume (adjusted OR = 4.0, 95% CI 1.50–10.7, p = 0.01). After restricting the analysis to the gonadotroph PitNET group, tumors with an IRS of 1–2 showed significantly higher invasiveness compared with those with an IRS of 3–6 (p = 0.012). These findings suggest that mE-cad may serve as a biomarker of PitNET invasiveness, with expression varying according to TF lineage and tumor subtype.

Pituitary neuroendocrine tumors (PitNETs), also known as pituitary adenomas, are rare tumors that are usually benign. At present, the WHO PitNET classification based on transcription factors is in force. A problem is caused by invasive tumors and silent tumors which, despite a lack of obvious clinical symptoms, tend to behave aggressively. Factors influencing the clinical course of these tumors are currently being sought. 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 PitNETs depending on the transcription factor and adenoma subtype. The analysis was performed in seventy-four patients operated on in a single neurosurgical center for pituitary tumors. Immunohistochemistry was performed for transcription factors and biomarkers—PD-L1, 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 p = 0.03). All tumors (100%) with a combination of cyclin D1 ≥ 10% and P53 < 10% were invasive on the Hardy scale. Of the four factors, PD-L1 increased the odds of invasiveness the most (adjusted OR = 2.35; 95% CI: 0.56–9.90). PD-L1 expression was present in some types of PitNETs. PD-L1 expression may help in identifying null cell adenomas. High cyclin D1 with low P53 may indicate greater tumor invasiveness.

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% & P5310% 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.

Background/Objective: Pituitary neuroendocrine tumors (PITNETs) often show a tendency towards invasive behavior, i.e., an invasion towards the cavernous sinuses or destruction of the sella turcica. In the present study, we analyzed whether a transcriptionally active HPV infection affects the invasiveness of pituitary tumors. Methods: Sixty patients with different phenotypes of PITNETs who underwent neurosurgery were studied. The obtained postoperative material was analyzed histopathologically. For each patient, formalin-fixed paraffin-embedded blocks were cut into ultra-thin slices and two to three of them were designated for DNA extraction, while one was used for histological slides. Based on the isolated DNA, the presence of DNA from individual HPV types was determined by the real-time detection polymerase chain reaction using the REALQUALITY RQ-Multi HPV Detection reagent kit (AB ANALITICA, Italy). P16 protein expression was assessed by immunohistochemical staining on the histological slides. A transcriptionally active infection with individual HPV types was distinguished when HPV DNA and P16 protein overexpression were detected simultaneously for a given tumor. Results: In the group of the 60 analyzed PITNETs, a transcriptionally active high-risk HPV infection was detected in a subset of 11 tumors (18.3%). This infection was associated with a significantly lower probability of tumor invasiveness, measured on both the Knosp (OR = 0.11, 95% CI: 0.02–0.58) and Hardy scales (OR = 0.12 95% CI: 0.024–0.56). Conclusions: Further studies are needed to confirm the prevalence of transcriptionally active HPV infections in pituitary adenomas and the role of these infections in the invasiveness of pituitary tumors.