Expression of follicle-stimulating hormone receptor by the vascular endothelium in tumor metastases

Abstract

BackgroundThe Follicle Stimulating Hormone receptor (FSHR) is expressed by the vascular endothelium in a wide range of human tumors. It was not determined however if FSHR is present in metastases which are responsible for the terminal illness.MethodsWe used immunohistochemistry based on a highly FSHR-specific monoclonal antibody to detect FSHR in cancer metastases from 6 major tumor types (lung, breast, prostate, colon, kidney, and leiomyosarcoma ) to 6 frequent locations (bone, liver, lymph node, brain, lung, and pleura) of 209 patients.ResultsIn 166 patients examined (79%), FSHR was expressed by blood vessels associated with metastatic tissue. FSHR-positive vessels were present in the interior of the tumors and some few millimeters outside, in the normally appearing tissue. In the interior of the metastases, the density of the FSHR-positive vessels was constant up to 7 mm, the maximum depth available in the analyzed sections. No significant differences were noticed between the density of FSHR-positive vessels inside vs. outside tumors for metastases from lung, breast, colon, and kidney cancers. In contrast, for prostate cancer metastases, the density of FSHR-positive vessels was about 3-fold higher at the exterior of the tumor compared to the interior. Among brain metastases, the density of FSHR-positive vessels was highest in lung and kidney cancer, and lowest in prostate and colon cancer. In metastases of breast cancer to the lung pleura, the percentage of blood vessels expressing FSHR was positively correlated with the progesterone receptor level, but not with either HER-2 or estrogen receptors. In normal tissues corresponding to the host organs for the analyzed metastases, obtained from patients not known to have cancer, FSHR staining was absent, with the exception of approx. 1% of the vessels in non tumoral temporal lobe epilepsy samples.ConclusionFSHR is expressed by the endothelium of blood vessels in the majority of metastatic tumors.

Hormone signaling pathways as treatment targets in renal cell cancer (Review)

“…The FSH receptor (FSHR), which was expected to be expressed only in the ovary and testis, was recently detected in the blood vessels of many solid tumors, including RCC (54,55). FSHR expression was evaluated in the endothelium of 1,336 primary solid tumors, representing 11 tumor types, comprised mostly of genitourinary malignancies and 64 RCC cases.…”

Gonadotropin-releasing hormone antagonist: A real advantage?

“…Both direct and indirect mechanisms may be involved for growth of PCa. FSH receptor is selectively expressed on the surface of the blood vessels of a wide range of tumors and metastatic sites including PCa [12,13], and it appears that FSH receptors and their ligands may play a role in the regulation of PCa growth. FSH receptor is also expressed in bone, where they accelerate bone resorption [14].…”

The endocrine influence on the bone microenvironment in early breast cancer

“…FSH has effects on HSC in bone, with evidence from in vivo models that bone-derived HSC express FSH receptor and that treatment with FSH enhances haematopoetic recovery after chemotherapy (Shaikh et al 2016). FSH also influences the vasculature; the FSH receptor (not normally expressed on vascular endothelium) is upregulated in the vasculature of bone metastases (Siraj et al 2013). The influence of FSH on bone mass has also been linked to its effects on the immune system; production of boneresorbing cytokines and bone mineral density (BMD) was evaluated in 36 healthy women (aged 20-50) and showed BMD was inversely proportional to FSH levels and endogenous FSH levels correlated with circulating levels of IL-1beta.…”