Expression and subcellular localization of CRH and its receptors in human endometrial cancer

Abstract

CRH and its receptors are expressed in human normal endometrial cells, where they are associated to anti-proliferative progesterone-like activity. We aimed to investigate CRH, CRH-R1 and CRH-R2 expression and intracellular localization in human endometrial cancers and their relationships with tumor biological parameters. Surgical specimens were obtained from 51 untreated endometrial cancer patients and immunohistochemistry for CRH, CRH receptors, ER, PR and Ki-67 was performed. We found a diffuse cytoplasmic staining in 100%, 92 % and 60.7 % of tumor specimens for CRH, CRH-R1 and R2, respectively. At variance with tumor tissues, the surrounding normal endometrial glands exhibit a typical paranuclear/apical pattern for CRH and stained for CRH-R2 at the nuclear level, whereas CRH-R1 staining was similar to that observed in tumor area. Positive correlations were found between CRH-R1 and PR expression, as well as between CRH-R2 cytoplasmic pattern and more advanced FIGO stage disease, respectively.

The corticotropin releasing factor system in cancer: expression and pathophysiological implications

“…The surrounding normal endometrial glands showed a typical paranuclear/apical pattern for CRF and stained for CRF2 receptor at the nuclear level, whereas CRF1 receptor staining was similar to that observed in tumors. CRF2 cytoplasmic pattern was associated with more advanced FIGO stage disease [34,35]. In contrast, positive correlation was found between CRF1 and progesterone receptor expression suggesting a potential role of this receptor in the characterization of less aggressive tumors.…”

Different effects of corticotropin-releasing factor and urocortin 2 on apoptosis of prostate cancer cells in vitro

“…Corticotropin-releasing factor (CRF) and Urocortin (Ucn) have been found to be over-expressed in human reproductive tumors such as ovarian cancer (Suda et al 1986), endometrial adenocarcinoma (Miceli et al 2009), and hydatidiform mole (Okamoto et al 1990). However, the special effects of CRF family peptides on cellular apoptosis in reproductive tumors are controversial at present.…”

Immunolocalization of Corticotropin-Releasing Hormone (CRH) and Its Receptors (CRHR1 and CRHR2) in Human Endometrial Carcinoma

“…Antigen-antibody complexes were visualized with 3,3′-diaminobenzidine (DAB) solution (1-mM DAB, 50-mM Tris–HCl buffer [pH 7.6], and 0.006% H 2 O 2 ) and counterstained with hematoxylin. Human placental tissue was used as a positive control for CRH, CRHR1, and CRHR2 immunostaining 14. As a negative control, normal goat or mouse immunoglobulin G was used instead of the primary antibody.…”

“…Of note, the expression of CRH and its receptors has also been reported in several types of carcinoma 12,13. Specifically, Miceli14 reported CRH, CRHR1, and CRHR2 immunoreactivity in endometrial carcinoma. Although stress is known to be a promoter of tumor growth,15 it remains unclear whether CRH, CRHR1, or CRHR2 immunoreactivity in endometrial carcinoma is a risk factor for poor prognosis.…”