Follicle-stimulating Hormone Touted as Promising New Tumor Marker

Follicle-stimulating hormone (FSH), which in human adults is expressed only in gonadal tissues, has been found to be present in 11 common tumor types where it may serve as a tumor marker and drug target.

Investigators at Mount Sinai School of Medicine (New York, NY, USA) and the [French] National Institute of Health and Medical Research (Paris, France) used immunohistochemical and immunoblotting techniques involving four separate FSH-receptor-specific monoclonal antibodies that recognized different FSH receptor epitopes and in situ hybridization to detect FSH receptor in tissue samples from patients with a wide range of tumors. Immunoelectron microscopy was used to detect FSH receptor in mouse tumors.

The investigators reported in the October 21, 2010, issue of the journal the New England Journal of Medicine (NEJM) that having screened 1336 patients, they could confirm that the FSH receptor was expressed by endothelial cells in tumors of all grades, including early T1 tumors. The tumors were located in the prostate, breast, colon, pancreas, urinary bladder, kidney, lung, liver, stomach, testis, and ovary. In specimens obtained during surgery performed to remove tumors, the FSH receptor was not expressed in the normal tissues located more than 10 mm from the tumors. The tumor lymphatic vessels did not express FSH receptor.

Immunoelectron microscopy in mice with xenograft tumors, after perfusion with anti–FSH-receptor antibodies coupled to colloidal gold, showed that the FSH receptor was exposed on the luminal endothelial surface and could bind and internalize circulating ligands.

"This new tumor marker may be used to improve cancer detection. Tumor imaging agents that bind to the new marker could be injected in the vasculature and would make visible early tumors located anywhere in the body using magnetic resonance imaging, positron emission tomography, or ultrasound imaging,” said first author Dr. Aurelian Radu, assistant professor of developmental and regenerative biology at the Mount Sinai School of Medicine. "New therapeutic agents can be developed that will block the tumor blood supply, either by inhibiting formation of new blood vessels, blocking the blood flow by coagulation, or by destroying the existing tumor vessels.”

"We are currently investigating the mechanism that leads to the abnormal presence of FSH-receptor on the cells that form the walls of the tumor blood vessels. Studies are in progress to assess the potential contribution of FSH receptor to tumor growth and its connection with known tumor signaling mechanisms, and to generate and evaluate in animals imaging and therapeutic agents,” said Dr. Radu.

Related Links:
Mount Sinai School of Medicine
National Institute of Health and Medical Research (INSERM)