Oncogene-Induced Senescence in Pituitary Adenomas

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Oncogene-Induced Senescence in Pituitary Adenomas—an Immunohistochemical Study

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作者：Emilija Manojlovic-Gacic ; Milica Skender-Gazibara ; Vera Popovic…
关键词：Pituitary adenoma ; Oncogene ; induced senescence ; GH adenomas granulation pattern ; Immunohistochemistry
刊名：Endocrine Pathology
出版年：2016
出版时间：March 2016
年：2016
卷：27
期：1
页码：1-11
全文大小：1,537 KB
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作者单位：Emilija Manojlovic-Gacic (1)
Milica Skender-Gazibara (1)
Vera Popovic (2) (3)
Ivan Soldatovic (3)
Novica Boricic (1)
Savo Raicevic (4)
Sandra Pekic (2) (3)
Mirjana Doknic (2) (3)
Dragana Miljic (2) (3)
Irina Alafuzoff (5) (6)
Fredrik Pontén (7)
Olivera Casar-Borota (5) (6)

1. Institute of Pathology, Medical Faculty, University of Belgrade, Dr Subotica 1, Belgrade, Serbia
2. Clinic of Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia, Dr Subotica 13, Belgrade, Serbia
3. Medical Faculty, University of Belgrade, Dr Subotica 8, Belgrade, Serbia
4. Neurosurgery Clinic, Clinical Center of Serbia, Koste Todorovica 4, Belgrade, Serbia
5. Department of Immunology, Genetics and Pathology, Uppsala University, Rudbeck Laboratory, Dag Hammarskjölds väg 20, Uppsala, Sweden
6. Department of Clinical Pathology and Cytology, Uppsala University Hospital, Rudbeck Laboratory, Dag Hammarskjölds väg 20, Uppsala, Sweden
7. Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Rudbeck Laboratory, Dag Hammarskjölds väg 20, Uppsala, Sweden
刊物主题：Pathology; Endocrinology; Oncology;
出版者：Springer US
ISSN：1559-0097

文摘

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. Keywords Pituitary adenoma Oncogene-induced senescence GH adenomas granulation pattern Immunohistochemistry