, Volume 22, Issue 2, pp 163–169 | Cite as

Filamin A and DRD2 expression in corticotrophinomas

  • Thais Sickler
  • Ericka Barbosa Trarbach
  • Fernando Pereira Frassetto
  • Juliano Bertollo Dettoni
  • Venâncio Avancini Ferreira Alves
  • Maria Candida Barisson Villares Fragoso
  • Marcio Carlos Machado
  • Ellison Fernando Cardoso
  • Marcello Delano Bronstein
  • Andrea GlezerEmail author



Filamin A (FLNA) expression is related to dopamine receptor type 2 (DRD2) expression in prolactinomas. Nevertheless, in corticotrophinomas, there are few studies about DRD2 expression and no data on FLNA. Therefore, we evaluated FLNA and DRD2 expression in corticotrophinomas and their association with tumor characteristics.


DRD2 and FLNA expression by immunohistochemistry, using H-score, based on the percentage of positive cells in a continuous scale of 0–300, were evaluated in 23 corticotrophinomas samples from patients submitted to neurosurgery. In six patients, treatment with cabergoline was indicated after non curative surgery.


Twenty-two patients were female and one male. Regarding tumor size, 10 were micro and 12 were macroadenomas. DRD2 expression was found in 89% of cases and did not correlate with FLNA expression. Moreover, the response to cabergoline, observed in 33% of the cases, did not correlate with DRD2 nor FLNA expression. FLNA expression was not associated with clinical and tumor characteristics, except for sphenoid sinus invasion.


In our cohort of corticotrophinomas, DRD2 expression was not associated with FLNA expression nor to the response to CAB. Nonetheless, FLNA expression could be related to tumor invasiveness.


Filamin A DRD2 Corticotrophinomas Cushing’s disease Cabergoline 



We specially thank Alda Wakamatsu for her carefully help in immunohistochemistry reactions. This work was supported by the National Council of Scientific and Technological Development (CNPq), number 162014/2013-9 and Federico Foundation.

Compliance with ethical standards

Conflict of interest

The authors declare that have no conflict of interest.

Ethical approval

This study was approved by the ethics committee and was performed in accordance with the ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.


  1. 1.
    Trouillas J, Roy P, Sturm N, Dantony E, Cortet-Rudelli C, Viennet G et al (2013) A new prognostic clinicopathological classification of pituitary adenomas: a multicentric case-control study of 410 patients with 8 years post-operative follow-up. Acta Neuropathol 126(1):123–135CrossRefGoogle Scholar
  2. 2.
    Lindholm J, Juul S, Jorgensen JOL, Astrup J, Bjerre P, Feldt-Rasmussen U et al (2001) Incidence and late prognosis of Cushing’s syndrome: a population-based study. J Clin Endocrinol Metab 86(1):117–123Google Scholar
  3. 3.
    Pivonello R, Faggiano A, Lombardi G, Colao A (2005) The metabolic syndrome and cardiovascular risk in Cushing’s syndrome. Endocrinol Metab Clin N Am 34(2):327–339CrossRefGoogle Scholar
  4. 4.
    Solak M, Kraljevic I, Dusek T, Melada A, Kavanagh MM, Peterkovic V et al (2016) Management of Cushing’s disease: a single-center experience. Endocrine 51(3):517–523CrossRefGoogle Scholar
  5. 5.
    Machado MC, Alcantara AEE, Pereira ACL, Cescato VAS, Musolino NRC, de Mendonca BB et al (2016) Negative correlation between tumour size and cortisol/ACTH ratios in patients with Cushing’s disease harbouring microadenomas or macroadenomas. J Endocrinol Investig 39(12):1401–1409CrossRefGoogle Scholar
  6. 6.
    Nieman LK, Biller BMK, Findling JW, Murad MH, Newell-Price J, Savage MO et al (2015) Treatment of Cushing’s syndrome: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 100(8):2807–2831CrossRefGoogle Scholar
  7. 7.
    Cuevas-Ramos D, Fleseriu M (2016) Medical treatment of Cushing’s disease. Minerva Endocrinol 41(3):324–340Google Scholar
  8. 8.
    Pivonello R, De Martino MC, De Leo M, Lombardi G, Colao A (2008) Cushing’s syndrome. Endocrinol Metab Clin N Am 37(1):135–149CrossRefGoogle Scholar
  9. 9.
    Pivonello R, Ferone D, de Herder WW, Kros JM, De Caro MLD, Arvigo M et al (2004) Dopamine receptor expression and function in corticotroph pituitary tumors. J Clin Endocrinol Metab 89(5):2452–2462CrossRefGoogle Scholar
  10. 10.
    Pivonello R, De Martino MC, Cappabianca P, De Leo M, Faggiano A, Lombardi G et al (2009) The medical treatment of cushing’s disease: effectiveness of chronic treatment with the dopamine agonist cabergoline in patients unsuccessfully treated by surgery. J Clin Endocrinol Metab 94(1):223–230CrossRefGoogle Scholar
  11. 11.
    Godbout A, Manavela M, Danilowicz K, Beauregard H, Bruno OD, Lacroix A (2010) Cabergoline monotherapy in the long-term treatment of Cushing’s disease. Eur J Endocrinol 163(5):709–716CrossRefGoogle Scholar
  12. 12.
    Lila AR, Gopal RA, Acharya SV, George J, Sarathi V, Bandgar T et al (2010) Efficacy of cabergoline in uncured (persistent or recurrent) cushing disease after pituitary surgical treatment with or without radiotherapy. Endocrine Pract 16(6):968–976CrossRefGoogle Scholar
  13. 13.
    Vilar L, Naves LA, Azevedo MF, Arruda MJ, Arahata CM, Silva LME et al (2010) Effectiveness of cabergoline in monotherapy and combined with ketoconazole in the management of Cushing’s disease. Pituitary 13(2):123–129CrossRefGoogle Scholar
  14. 14.
    Ferriere A, Cortet C, Chanson P, Delemer B, Caron P, Chabre O et al (2017) Cabergoline for Cushing’s disease: a large retrospective multicenter study. Eur J Endocrinol 176(3):305–314CrossRefGoogle Scholar
  15. 15.
    Peverelli E, Mantovani G, Vitali E, Elli FM, Olgiati L, Ferrero S et al (2012) Filamin-A is essential for dopamine D2 receptor expression and signaling in tumorous lactotrophs. J Clin Endocrinol Metab 97(3):967–977CrossRefGoogle Scholar
  16. 16.
    Peverelli E, Giardino E, Treppiedi D, Vitali E, Cambiaghi V, Locatelli M et al (2014) Filamin A (FLNA) plays an essential role in somatostatin receptor 2 (SST2) signaling and stabilization after agonist stimulation in human and rat somatotroph tumor cells. Endocrinology 155(8):2932–2941CrossRefGoogle Scholar
  17. 17.
    Knosp E, Steiner E, Kitz K, Matula C (1993) Pituitary-adenomas with invasion of the cavernous sinus space—a magnetic-resonance-imaging classification compared with surgical findings. Neurosurgery 33(4):610–618Google Scholar
  18. 18.
    Hardy J, Vezina JL (1976) Transsphenoidal neurosurgery of intracranial neoplasm. Adv Neurol 15:261–273Google Scholar
  19. 19.
    Jordan RC, Lingen MW, Perez-Ordonez B, He X, Pickard R, Koluder M et al (2012) Validation of methods for oropharyngeal cancer HPV status determination in US cooperative group trials. Am J Surg Pathol 36(7):945–954CrossRefGoogle Scholar
  20. 20.
    Mancini T, Casanueva FF, Giustina A (2008) Hyperprolactinemia and prolactinomas. Endocrinol Metab Clin N Am 37(1):67–99CrossRefGoogle Scholar
  21. 21.
    Shao QQ, Zhang TP, Zhao WJ, Liu ZW, You L, Zhou L et al (2016) Filamin A: insights into its exact role in cancers. Pathol Oncol Res 22(2):245–252CrossRefGoogle Scholar
  22. 22.
    Bachmann AS, Howard JP, Vogel CW (2006) Actin-binding protein filamin A is displayed on the surface of human neuroblastoma cells. Cancer Sci 97(12):1359–1365CrossRefGoogle Scholar
  23. 23.
    Coughlin MF, Puig-de-Morales M, Bursac P, Mellema M, Millet E, Fredberg JJ (2006) Filamin-A and rheological properties of cultured melanoma cells. Biophys J 90(6):2199–2205CrossRefGoogle Scholar
  24. 24.
    Zhu TN, He HJ, Kole S, D’Souza T, Agarwal R, Morin PJ et al (2007) Filamin A-mediated down-regulation of the exchange factor Ras-GRF1 correlates with decreased matrix metalloproteinase-9 expression in human melanoma cells. J Biol Chem 282(20):14816–14826CrossRefGoogle Scholar
  25. 25.
    Jiang X, Yue JY, Lu HM, Campbell N, Yang QF, Lan SJ et al (2013) Inhibition of filamin-A reduces cancer metastatic potential. Int J Biol Sci 9(1):67–77CrossRefGoogle Scholar
  26. 26.
    Sun GG, Sheng SH, Jing SW, Hu WN (2014) An antiproliferative gene FLNA regulates migration and invasion of gastric carcinoma cell in vitro and its clinical significance. Tumor Biol 35(3):2641–2648CrossRefGoogle Scholar
  27. 27.
    Savoy RM, Ghosh PM (2013) The dual role of filamin A in cancer: can’t live with (too much of) it, can’t live without it. Endocr Relat Cancer 20(6):R341–R356CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Thais Sickler
    • 1
  • Ericka Barbosa Trarbach
    • 1
  • Fernando Pereira Frassetto
    • 2
  • Juliano Bertollo Dettoni
    • 3
  • Venâncio Avancini Ferreira Alves
    • 2
  • Maria Candida Barisson Villares Fragoso
    • 1
  • Marcio Carlos Machado
    • 1
    • 4
  • Ellison Fernando Cardoso
    • 5
  • Marcello Delano Bronstein
    • 1
  • Andrea Glezer
    • 1
    • 6
    Email author
  1. 1.Neuroendocrine Unit, Division of Endocrinology and Metabolism, Hospital das Clínicas & Laboratory of Cellular and Molecular Endocrinology LIM-25University of Sao Paulo Medical SchoolSão PauloBrazil
  2. 2.Pathology Unit, Hospital das Clínicas & Laboratory of Pathology, LIM-14University of Sao Paulo Medical SchoolSão PauloBrazil
  3. 3.Hospital Universitário Cassiano Antonio de Moraes/UFESVitóriaBrazil
  4. 4.Endocrinology ServiceAC Camargo Cancer CenterSão PauloBrazil
  5. 5.Department of Radiology, LIM-44University of Sao Paulo Medical SchoolSão PauloBrazil
  6. 6.Medical SchoolUniversity of Sao PauloSão PauloBrazil

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