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

Krzentowska, Anna; Biesaga, Beata; Czepko, Ryszard; Merklinger-Gruchała, Anna; Adamek, Dariusz; Jasińska, Małgorzata; Pluta, Barbara; Michalska, Wiktoria; Wróblewska, Katarzyna; Janczy, Filip; Gołkowski, Filip

doi:10.3390/ijms26167830

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

by

Anna Krzentowska

^1,*

,

Beata Biesaga

²,

Ryszard Czepko

³,

Anna Merklinger-Gruchała

²,

Dariusz Adamek

⁴,

Małgorzata Jasińska

⁵

,

Barbara Pluta

⁶,

Wiktoria Michalska

⁶,

Katarzyna Wróblewska

⁶,

Filip Janczy

⁶ and

Filip Gołkowski

¹

Department of Endocrinology and Internal Medicine, Medical College, Andrzej Frycz Modrzewski Krakow University, 30-705 Kraków, Poland

²

Faculty of Health Sciences, Medical College, Andrzej Frycz Modrzewski Krakow University, 30-705 Kraków, Poland

³

Department of Neurosurgery, Medical College, Andrzej Frycz Modrzewski Krakow University, 30-705 Kraków, Poland

⁴

Department of Neuropathology, and Chair and Department of Pathomorphology, Faculty of Medicine, Jagiellonian University Medical College, 31-008 Kraków, Poland

⁵

Department of Histology, Jagiellonian University Medical College, 31-008 Kraków, Poland

⁶

Students’ Scientific Interest Group, Medical College, Andrzej Frycz Modrzewski Krakow University, 30-705 Kraków, Poland

^*

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2025, 26(16), 7830; https://doi.org/10.3390/ijms26167830

Submission received: 6 July 2025 / Revised: 9 August 2025 / Accepted: 12 August 2025 / Published: 13 August 2025

(This article belongs to the Special Issue Biomarkers in Cancer Immunology)

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Abstract

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 <3% and ≥3%, and the expression of P53 and cyclin D1 was scored at <10% and ≥10%. The following tumors expressed PD-L1 at ≥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 tumor, 1 (1.3%); mature PIT-1 tumor, 1 (1.5%). KI ≥ 3% was found in the following 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%); and mature PIT-1 tumor, 1 (1.3%). Patients with K ≥ 3% were statistically significantly younger (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.

Keywords: biomarkers; PD-L1; Ki-67; Cyclin D1; P53; PitNETs; transcription factors; invasiveness

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MDPI and ACS Style

Krzentowska, A.; Biesaga, B.; Czepko, R.; Merklinger-Gruchała, A.; Adamek, D.; Jasińska, M.; Pluta, B.; Michalska, W.; Wróblewska, K.; Janczy, F.; et al. The Roles of PD-L1, Ki-67, P53, and Cyclin D1 in PitNETs: Diagnostic and Prognostic Implications in a Series of 74 Patients. Int. J. Mol. Sci. 2025, 26, 7830. https://doi.org/10.3390/ijms26167830

AMA Style

Krzentowska A, Biesaga B, Czepko R, Merklinger-Gruchała A, Adamek D, Jasińska M, Pluta B, Michalska W, Wróblewska K, Janczy F, et al. The Roles of PD-L1, Ki-67, P53, and Cyclin D1 in PitNETs: Diagnostic and Prognostic Implications in a Series of 74 Patients. International Journal of Molecular Sciences. 2025; 26(16):7830. https://doi.org/10.3390/ijms26167830

Chicago/Turabian Style

Krzentowska, Anna, Beata Biesaga, Ryszard Czepko, Anna Merklinger-Gruchała, Dariusz Adamek, Małgorzata Jasińska, Barbara Pluta, Wiktoria Michalska, Katarzyna Wróblewska, Filip Janczy, and et al. 2025. "The Roles of PD-L1, Ki-67, P53, and Cyclin D1 in PitNETs: Diagnostic and Prognostic Implications in a Series of 74 Patients" International Journal of Molecular Sciences 26, no. 16: 7830. https://doi.org/10.3390/ijms26167830

APA Style

Krzentowska, A., Biesaga, B., Czepko, R., Merklinger-Gruchała, A., Adamek, D., Jasińska, M., Pluta, B., Michalska, W., Wróblewska, K., Janczy, F., & Gołkowski, F. (2025). The Roles of PD-L1, Ki-67, P53, and Cyclin D1 in PitNETs: Diagnostic and Prognostic Implications in a Series of 74 Patients. International Journal of Molecular Sciences, 26(16), 7830. https://doi.org/10.3390/ijms26167830

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

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