Gonadotropin-releasing hormone neuropeptides and receptor in human breast cancer: correlation to poor prognosis parameters.

Expression of the two gonadotropin-releasing hormone homologue peptides GnRHI and GnRHII and their receptor GnRHR has been demonstrated in a number of malignancies. In hormone-dependent breast cancer, GnRH analogs are used for therapy in premenopausal women. Gene expression of GnRHI, II and R was studied in breast biopsies from primary breast adenocarcinoma obtained from the tumor and the adjacent benign tissue. Levels were evaluated by a multiplex real-time RT-PCR. GnRHI transcripts were detected in 14.7% of the benign and 29.4% malignant biopsies and GnRHII in 21.2% benign and 44.1% malignant biopsies. GnRHR was also more frequent in the malignant (54.2%) than in the benign (24.0%) biopsies, at similar expression levels. No transcripts were detected in biopsies from healthy individuals. There was a strong correlation between the presence of GnRHI and GnRHII transcripts and their receptor in the benign and the malignant biopsies. GnRHI, II and R expression correlated significantly with poor prognosis pathological parameters. Immunohistochemistry for GnRHR revealed expression in malignant cells and in epithelial cells of mammary ducts of the adjacent area with pre-cancerous features. In contrast, GnRH I and II peptides were rarely expressed at low levels in breast cancer cells. In conclusion GnRH peptides and receptor are expressed more frequently in breast tumors than in the adjacent mammary tissue, representing a malignant feature. Their expression correlated to tumor characteristics of poor prognosis and was therefore related to more aggressive malignancies. Concomitant expression of peptides and receptor supports an autocrine/paracrine regulating role.