INCREASED NUMBER OF ACTIVATED MAST CELLS IN ENDOMETRIOSIS LESIONS

E.J. Stanford,¹ D. Kempuraj,² N. Papadopoulou,² S. Christodoulou,¹ B. Madhappen,² G. Sant,² T.C. Theoharides²

¹ St. Mary’s-Good Samaritan Hospital, Centralia, IL

² Tufts University School of Medicine and Tufts-New England Medical Center, Boston, MA

OBJECTIVE: Endometriosis is a common debilitating chronic pain disorder of women.  The inciting chemical events responsible for pain and fibrosis in endometriosis are not clear yet may involve increased numbers of mast cells with associated mast cell activation.  This study examines the quantity of mast cells in biopsy-proven endometriosis implants and their level of activation.

MATERIALS AND METHODS:  Biopsy-proven endometriosis implants (n=10) and normal unaffected peritoneal tissue (n=3) were immunostained for mast cell tryptase, a commonly used test to determine the number of mast cells and their level of activation.  The color of the endometriosis implants noted at laparoscopy was compared for mast cell number and activation.

RESULTS: Patients in this study had failed medical therapy, including hormonal treatment for at least 3 months with no relief of symptoms. They had also not undergone any prior surgical procedures for at least one year.  Biopsy-proven human endometriosis implants, confirmed by an independent pathologist, were found to have increased numbers of tryptase positive mast cells (64 - 157 mast cells/mm2) with a high level of activation (89%).  Standardized techniques for calculating mast cell number and levels of activation were used.  Higher activation was noted in areas that stained strongly positive for Urocortin (Ucn).  Normal unaffected peritoneum had few mast cells and weak activation (<10%).  There was a difference noted in the number of mast cells and their associated activation when the color of the lesions was compared.  Dark lesions (brown or black) had more mast cells and were more highly activated compared to red or clear lesions.

CONCLUSIONS: Mast cells are responsible for inflammation and fibrosis both of which are characteristics of endometriosis.  Biopsy-proven endometriosis implants were found to have higher numbers of activated mast cells particularly darker, more fibrotic, implants.  The mechanism by which activated mast cells contribute to the fibrosis and inflammation of endometriosis may be associated with higher Ucn.

Disclosure - Grant/Research: E.J. Stanford, Ortho-McNeil; Advisory Board: E.J. Stanford, Ortho-McNeil.