, Volume 64, Issue 1, pp 147–156 | Cite as

Hormonal aggressiveness according to the expression of cellular markers in corticotroph adenomas

  • Jung Soo Lim
  • Mi-Kyung Lee
  • Eunhee Choi
  • Namki Hong
  • Soo Il Jee
  • Sun Ho KimEmail author
  • Eun Jig LeeEmail author
Original Article



The molecular mechanisms underlying tumor growth in Cushing’s disease (CD) still remain a challenge. Moreover, clinical manifestations of CD may vary depending on hormonal activity; however, factors involved in the hormonal aggressiveness of adrenocorticotropic hormone (ACTH)-secreting pituitary tumors have not been fully clarified. We investigated the association between the expression of cellular markers regarding pituitary tumor progression and initial or postoperative hormone levels in patients with CD.


Tumor tissues from 28 corticotroph adenomas (female 26, male 2, mean age 39.21 ± 10.39 years) were subject to immunohistochemical study using the following antibodies: pituitary tumor-transforming gene 1 (PTTG1), cyclin D1, p16, p27, brahma related-gene 1 (Brg1), and Ki-67. We then analyzed the relationship between each cellular marker expression and hormone levels, including 24 h urinary free cortisol (UFC), plasma ACTH, and serum cortisol.


PTTG1 and Ki-67 were expressed in 100% and 50% of patients, respectively. However, the levels did not reflect initial hormonal activity. The cyclin D1-negative group showed higher serum cortisol levels compared to the cyclin D1-positive group (p = 0.01). The 24 h UFC levels were significantly higher in the p27-negative group than in the p27-positive group (p = 0.04), whereas the Brg1-positive group revealed higher serum cortisol levels than in the Brg1-negative group (p = 0.02).


Although PTTG1 and Ki-67 play an essential role in developing ACTH-secreting tumors, cyclin D1, p27, and Brg1 may be better biomarkers to determine hormonal aggressiveness of the tumor. Further research is needed to understand the influence of cellular markers on hormonal activity in CD.


Cushing syndrome ACTH-secreting pituitary adenoma Hormones Biomarkers 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

12020_2018_1815_MOESM1_ESM.docx (41 kb)
Supplemental Tables
12020_2018_1815_MOESM2_ESM.docx (56 kb)
Supplemental Fig. 1


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Internal Medicine, Institute of Evidence-based MedicineYonsei University Wonju College of MedicineWonjuSouth Korea
  2. 2.Department of PathologyNational Health Insurance Service, Ilsan HospitalGoyangSouth Korea
  3. 3.Smith Center for Outcomes Research in CardiologyBeth Israel Deaconess Medical CenterBostonUSA
  4. 4.Department of Internal MedicineYonsei University College of MedicineSeoulSouth Korea
  5. 5.Neurosurgery and Yonsei Brain Research InstituteYonsei University College of MedicineSeoulSouth Korea

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