EXPRESSION OF HEPARANASE IN UTEROSACRAL LIGAMENTS OF WOMEN WITH OR WITHOUT UTERINE PROLPASE
BEN ZVI1, L. SCHREIBER 2, R. SAGIV 1, J. BAR 1, S. GINATH 1;
1Obstetrics and Gynecology, Wolfson Med. Ctr., Sackler Faculty of Med., Tel Aviv Univ., Holon, Israel, 2Pathology, Wolfson Med. Ctr., Holon, Israel.
Introduction: Pelvic organ prolapse (POP) is a global health problem for which the pathophysiological mechanism remains to be elucidated. The loss of extracellular matrix proteins is considered to be important in the molecular basis of this pathology. Heparanase is a heparin sulfate degrading endoglycosidase that has important roles in various biological processes, including proteoglycan degradation, and is a key component of the extracellular matrix.
Objective: The objective of this study was to compare expression of Heparanase in connective tissue of uterosacral ligaments in women with or without uterine prolapse.
Methods: Thirty-nine women who underwent hysterectomy for benign reasons enrolled in this study. Twenty-three women underwent vaginal hysterectomy (VH) for uterine prolapse (stage ≥3) and sixteen women underwent abdominal hysterectomy for fibroid uterus without uterine prolapse (stage <2). Uterosacral ligaments biopsies were obtained from all uterine specimens near its origin. All tissue samples were analyzed by immunohistochemistry with regard to presence of heparanase using antiheparanse antibody 733.
Results: Heparanse positive staining was more common in the connective tissue of uterosacral ligaments in women with uterine prolapse. Positive staining was seen in 17/23 (73%) women with uterine prolapse compared to 4/16 (25%) without uterine prolapse (p = 0.007). In women with uterine prolapse heparanase immunostaining was noted as brown gargle (arrow) in the cytoplasmatic portion of the fibroblasts in the uterosacral ligaments (Figure 1 A). In women without prolapse absence of such delicate sign was more common (Figure 1 B). On multivariate logistic regression analysis, positive staining was independently associated with VH, even after controlling for women's age.
Conclusions: Heparanase expression is more common in the connective tissue of uterosacral ligaments in women with uterine prolapse compared to normal, suggesting its role in the pathological processes of compromising pelvic floor function and the development of uterine prolapse.