Follicle-stimulating hormone (FSH) is a molecule that is typically associated with the growth and development of ovarian follicles. However, in a recent study published in the New England Journal of Medicine, researchers explored whether the FSH receptor is also found in the blood vessels that feed a variety of human tumors. The rationale for this study was the observation that although FSH receptors are most commonly found in ovarian granulosa and testicular Sertoli cells, low level expression has also been seen in the endothelial cells that line the ovarian and testicular blood vessels. This prompted them to ask whether the FSH receptor might aberrantly be found in other blood vessels during times of tumor growth.

Ghinea, et al studied tissue from 1,336 treatment-naïve patients with a variety of tumor types. Using a combination of antibody and in situ hybridization techniques, combined with electron microscopy, they initially examined FSHR expression in prostate tumors that formed in mice, they found strong expression at the blood vessel endothelial cells found at the periphery of the tumors, and never in normal prostate tissue. They then expanded their search to a wide variety of paraffin-fixed human tumor types, including breast, colon, pancreas, bladder, kidney and lung. Without exception, FSHR expression was found in the blood vessels at the periphery of the tumor, and again not in normal tissue. They also examined FSHR in a variety of inflammatory states such as chronic pancreatitis, and did not regularly see FSHR, suggesting that this finding is reasonably tumor-specific.

The clinical implications of these findings is that the FSHR receptor may be an important target for both tumor imaging as well as treatment. From an imaging standpoint, because the receptor is most densely expressed at the tumor periphery, it implies that in vivo identification of the FSHR may provide a novel, very specific way to delineate the normal versus tumor tissue boundary, which would vastly improve our ability to stage tumors preoperatively and non-invasively. The molecular implications of FSHR expression on tumor vessels is not yet clear, but one intriguing observation is that the binding of FSH to its receptor leads to an upregulation of HIF-1alpha, which in turn upregulates the VEGF that is necessary for tumor angiogenesis. This makes it logical to consider therapies that aim to simultaneously block FSH and VEGF signaling. While very early days, this study adds yet a new marker and target to the growing number of molecular abnormalities in cancer.