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Immunolocalization of Corticotropin-Releasing Hormone (CRH) and Its Receptors (CRHR1 and CRHR2) in Human Endometrial Carcinoma: CRHR1 as a Potent Prognostic Factor
  1. Naoko Sato, PhD,
  2. Kiyoshi Takagi, PhD,
  3. Takashi Suzuki, MD, PhD,
  4. Yasuhiro Miki, PhD,
  5. Sota Tanaka, MD, PhD,
  6. Satoru Nagase, MD, PhD,
  7. Hitoshi Warita, MD, PhD,
  8. Shin Fukudo, MD, PhD,
  9. Fumiko Sato, PhD,
  10. Hironobu Sasano, MD, PhD and
  11. Kiyoshi Ito, MD, PhD
  1. Tohoku University Graduate School of Medicine, Sendai, Japan.
  1. Address correspondence and reprint requests to Kiyoshi Ito, MD, Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Sendai, 980–8557 Japan. E-mail:


Objective Corticotropin-releasing hormone (CRH), a major regulator of the stress response, regulates various biological functions through its interaction with CRH receptors 1 (CRHR1) and 2 (CRHR2). CRH, CRHR1, and CRHR2 have recently been reported in several types of carcinoma, but the significance of these proteins has remained largely unknown in human endometrial carcinoma.

Materials and Methods A total of 87 endometrial carcinoma specimens were obtained from Japanese female patients who underwent surgical treatment, fixed in 10% formalin, and embedded in paraffin wax. Immunohistochemistry for CRH, CRHR1, and CRHR2 was performed, and clinical data were obtained from the medical records.

Results Immunopositivity of CRH, CRHR1, and CRHR2 in the specimens was 26%, 15%, and 10%, respectively. Univariate analysis revealed that immunohistochemical CRH status was positively associated with CRHR1 and CRHR2 status and that CRHR1 status was significantly associated with the risk of recurrence and poorer clinical outcome, whereas CRHR2 status was marginally associated with better prognosis for overall survival. Multivariate analysis demonstrated CRHR1 status as an independent prognostic factor for both disease-free and overall survival.

Conclusions These results suggest that intratumoral CRH-CRHR1 signaling plays an important role in the progression of endometrial carcinoma and that CRHR1 is a potent prognostic factor in patients with this disease.

  • Corticotropin-releasing hormone
  • Corticotropin-releasing hormone receptor 1
  • Endometrial cancer
  • Immunohistochemistry
  • Prognosis

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  • This research was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology and the Ministry of Health, Labour and Welfare, Japan.

  • ThinkSCIENCE K.K. ( provided editing services, which were funded by the grants.

  • Supplemental digital content is available for this article. Direct URL citation appears in the printed text and is provided in the HTML and PDF versions of this article on the journal’s Web site (

  • The authors declare no conflicts of interest.

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