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Endocrine Pathology

, Volume 27, Issue 1, pp 1–11 | Cite as

Oncogene-Induced Senescence in Pituitary Adenomas—an Immunohistochemical Study

  • Emilija Manojlovic-Gacic
  • Milica Skender-Gazibara
  • Vera Popovic
  • Ivan Soldatovic
  • Novica Boricic
  • Savo Raicevic
  • Sandra Pekic
  • Mirjana Doknic
  • Dragana Miljic
  • Irina Alafuzoff
  • Fredrik Pontén
  • Olivera Casar-Borota
Article

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.

Keywords

Pituitary adenoma Oncogene-induced senescence GH adenomas granulation pattern Immunohistochemistry 

Notes

Acknowledgments

This work was supported by the Ministry of Education and Science of Republic of Serbia, Grant No 175033. Part of this study performed within the Human Protein Atlas was supported by funding from the Knut and Alice Wallenberg Foundation. We thank Dijana Cerjan for assistance with the immunohistochemical analysis of beta-galactosidase.

Compliance with Ethical Standards

Conflict of Interest

Authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • 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. 1.Institute of Pathology, Medical FacultyUniversity of BelgradeBelgradeSerbia
  2. 2.Clinic of Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of SerbiaBelgradeSerbia
  3. 3.Medical FacultyUniversity of BelgradeBelgradeSerbia
  4. 4.Neurosurgery Clinic, Clinical Center of SerbiaBelgradeSerbia
  5. 5.Department of Immunology, Genetics and PathologyUppsala UniversityUppsalaSweden
  6. 6.Department of Clinical Pathology and CytologyUppsala University HospitalUppsalaSweden
  7. 7.Department of Immunology, Genetics and Pathology, Science for Life Laboratory Uppsala UniversityUppsalaSweden

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