Progesterone Receptor Expression in Neurofibromas 1

Abstract Neurofibromas are benign tumors of the peripheral nerve sheath, whichoccur sporadically and in association with the common familial cancer syn-drome, neurofibromatosis type 1. There are intriguing links between thegrowth of neurofibromas and levels of circulating hormones: neurofibromasoften first appear around the time of puberty, increase in number and sizeduring pregnancy, and shrink after giving birth. We examined 59 humanneurofibromas for the expression of estrogen and progesterone receptors(PRs), because their ligands, estrogen and progesterone, were attractivecandidate hormones. The majority (75%) of neurofibromas expressed PR,whereas only a minority (5%) of neurofibromas expressed estrogen receptor.Within neurofibromas, PR was expressed by non-neoplastic tumor-associatedcells and not by neoplastic Schwann cells. We hypothesize that progesteronemay play an important role in neurofibroma growth and suggest that anti-progestins may be useful in the treatment of this tumor.

[1]  D. Burns,et al.  Neurofibromas in NF1: Schwann Cell Origin and Role of Tumor Environment , 2002, Science.

[2]  D. Gutmann,et al.  NF1 deletions in S-100 protein-positive and negative cells of sporadic and neurofibromatosis 1 (NF1)-associated plexiform neurofibromas and malignant peripheral nerve sheath tumors. , 2001, The American journal of pathology.

[3]  M. Schumacher,et al.  Progesterone stimulates Krox-20 gene expression in Schwann cells. , 2001, Brain research. Molecular brain research.

[4]  T. Jacks,et al.  NF1 Tumor Suppressor Gene Function Narrowing the GAP , 2001, Cell.

[5]  X. Estivill,et al.  Schwann cells harbor the somatic NF1 mutation in neurofibromas: evidence of two different Schwann cell subpopulations. , 2000, Human molecular genetics.

[6]  B. Scheithauer,et al.  Tumors of the peripheral nervous system , 1999 .

[7]  R. Mirsky,et al.  Schwann cells and their precursors emerge as major regulators of nerve development , 1999, Trends in Neurosciences.

[8]  P. Giangrande,et al.  The A and B isoforms of the human progesterone receptor: two functionally different transcription factors encoded by a single gene. , 1999, Recent progress in hormone research.

[9]  C. Wang,et al.  Male Reproductive Function , 1999, Mineralogical Society Series.

[10]  S. Koide,et al.  Mifepristone. Auxiliary therapeutic use in cancer and related disorders. , 1998, The Journal of reproductive medicine.

[11]  B. Korf,et al.  The diagnostic evaluation and multidisciplinary management of neurofibromatosis 1 and neurofibromatosis 2. , 1997, JAMA.

[12]  M. Schumacher,et al.  Demonstration of progesterone receptors in rat Schwann cells , 1996, The Journal of Steroid Biochemistry and Molecular Biology.

[13]  P. Gruss,et al.  Making of a Schwann. , 1996, Trends in genetics : TIG.

[14]  M. Schumacher,et al.  Progesterone synthesis and myelin formation by Schwann cells. , 1995, Science.

[15]  Totian Es.  Female reproductive function in thyroid pathology , 1994 .

[16]  P. Schwartz,et al.  Solitary pelvic neural tumors with high steroid receptor content. , 1985, Gynecologic oncology.

[17]  R. Giuffrè,et al.  Hormones and tumours in central nervous system (CNS): steroid receptors in primary spinal cord tumours. , 1984, Neurological research.

[18]  C. Beattie,et al.  Steroid receptors in tumors of nerve sheath origin , 1982, Journal of surgical oncology.

[19]  R. Martuza,et al.  Specific estradiol binding in schwannomas, meningiomas, and neurofibromas. , 1981, Neurosurgery.