GHRH Receptor Expression in Malignant Mixed Müllerian Tumors

Abstract

Malignant mixed Müllerian tumors (MMMTs) are aggressive malignant neoplasms with a high recurrence rate and poor prognosis. Despite advances in adjuvant therapies in recent years, the prognosis of these tumors has not improved. Growth hormone-releasing hormone (GHRH) is produced by a variety of malignant tumors and acts as a growth factor in an autocrine/paracrine manner. Its function requires the presence of its receptors to exert its effects on neoplastic cells. In this study, we evaluated the expression of GHRH receptors (GHRH-R) in a group of MMMTs. Thirty-one examples of MMMTs from endometrium, ovary, uterine tube, and pelvic peritoneum were retrieved from the files of Department of Pathology at the University of Miami, Jackson Memorial Hospital. Immunohistochemistry for GHRH-R was performed on paraffin sections and the staining results were evaluated separately in both epithelial and mesenchymal components of each tumor. The presence of pituitary type growth hormone-releasing hormone receptor mRNA and that of its biologically active splice variant were also evaluated by RT-PCR in 6 of the tumors. Positive immunohistochemical reaction for GHRH-R was detected in 30 tumors (96%). The epithelial and sarcomatous components were positive in 30 (96%), whereas one endometrial tumor was negative in both components. The mRNA for GHRH-R and its splice variant was found in all 6 tested tumors. This study shows that GHRH-R is expressed by the majority of MMMTs in both epithelial and mesenchymal components. This finding could potentially serve as a basis for therapeutic approaches using synthetic peptide antagonists of GHRH-R that have shown significant efficacy with minimal side effects in experimental models.

Prognostic role of HPV infection in esophageal squamous cell carcinoma

“…GH stimulates the production of the insulin-like growth factor I (IGF-I), which plays a major role in malignant transformation, metastasis and tumorigenesis in various cancers [36]. The presence of GHRH-R and its splice variants, on different types of cancer cell lines has been demonstrated [37][38][39]. In our study, we found association neither between GHRH-R expression and the HPV status, nor between GHRH-R expression and response to treatment.…”

Molecular classification and subtype-specific drug sensitivity research of uterine carcinosarcoma under multi-omics framework

“…Process of which may promote endometrial proliferation and participate in the pathogenesis of ovarian, endometrial cancer and endometriosis. Another research shows that GHRH-R expresses in the majority of MMMT and this discovery could potentially serve as a basis for therapies using synthetic peptide antagonists of GHRH-R [23][24][25] . Additionally, positive estrogen receptor (ER) expression is detected in part of patients with uterine sarcoma.…”