1. Oncogene-Induced Senescence in Pituitary Adenomas—an Immunohistochemical Study
- Author
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Dragana Miljic, Irina Alafuzoff, Savo Raicevic, Ivan Soldatovic, Vera Popovic, Milica Skender-Gazibara, Novica Boricic, Sandra Pekic, Fredrik Pontén, Mirjana Doknic, Emilija Manojlovic-Gacic, and Olivera Casar-Borota
- Subjects
Adenoma ,Adult ,Cyclin-Dependent Kinase Inhibitor p21 ,Male ,0301 basic medicine ,Senescence ,medicine.medical_specialty ,Adolescent ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,Growth hormone ,Pathology and Forensic Medicine ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Pituitary adenoma ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,Pituitary Neoplasms ,Cellular Senescence ,Cyclin-Dependent Kinase Inhibitor p16 ,Aged ,business.industry ,Oncogenes ,General Medicine ,Middle Aged ,beta-Galactosidase ,medicine.disease ,Immunohistochemistry ,digestive system diseases ,stomatognathic diseases ,030104 developmental biology ,Tissue Array Analysis ,030220 oncology & carcinogenesis ,Oncogene-induced senescence ,Female ,Cancer development ,business ,Hormone - Abstract
Oncogene-induced senescence (OIS) serves as an initial barrier to cancer development, being proposed as a possible explanation for the usually benign behavior of the pituitary adenomas. We aimed to explore the immunohistochemical expression of the OIS markers, senescence-associated lysosomal β-galactosidase (SA-β-GAL), p16, and p21 in different types of 345 pituitary adenomas and compared it with the expression in the normal pituitary and in the specimens from the repeated surgeries. SA-β-GAL was overexpressed in the pituitary adenomas, compared to the normal pituitaries. Growth hormone (GH) producing adenomas showed the strongest SA-β-GAL, with densely granulated (DG)-GH adenomas more reactive than the sparsely granulated (SG). Nuclear p21 was decreased in the adenomas, except for the SG-GH adenomas that had higher p21 than the normal pituitaries and the other adenomas. p16 was significantly lower in the adenomas, without type-related differences. SA-β-GAL was slightly lower and p16 slightly higher in the recurrences. Our findings indicate alterations of the senescence program in the different types of pituitary adenomas. Activation of senescence in the pituitary adenomas presents one possible explanation for their usually benign behavior, at least in the GH adenomas that show a synchronous increase of two OIS markers. However, subdivision into GH adenoma subtypes reveals differences that reflect complex regulatory mechanisms influenced by the interplay between the granularity pattern and the hormonal factors, with possible impact on the different clinical behavior of the SG- and DG-GH adenoma subtypes. p16 seems to have a more prominent role in the pituitary tumorigenesis than in the senescence. Recurrent growth in a subset of the pituitary adenomas is not associated with consistent changes in the senescence pattern.
- Published
- 2015
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