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

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Abstract

Purpose

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.

Methods

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.

Results

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).

Conclusions

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.

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Authors and Affiliations

  1. Department of Internal Medicine, Institute of Evidence-based Medicine, Yonsei University Wonju College of Medicine, Wonju, South Korea

    Jung Soo Lim

  2. Department of Pathology, National Health Insurance Service, Ilsan Hospital, Goyang, Gyeonggi-do, South Korea

    Mi-Kyung Lee & Soo Il Jee

  3. Smith Center for Outcomes Research in Cardiology, Beth Israel Deaconess Medical Center, Boston, USA

    Eunhee Choi

  4. Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea

    Namki Hong & Eun Jig Lee

  5. Neurosurgery and Yonsei Brain Research Institute, Yonsei University College of Medicine, Seoul, South Korea

    Sun Ho Kim

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  1. Jung Soo Lim
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  3. Eunhee Choi
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Correspondence to Sun Ho Kim or Eun Jig Lee.

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Lim, J.S., Lee, MK., Choi, E. et al. Hormonal aggressiveness according to the expression of cellular markers in corticotroph adenomas. Endocrine 64, 147–156 (2019). https://doi.org/10.1007/s12020-018-1815-x

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