Enhanced deoxyribonucleic acid damage and repair but unchanged apoptosis in uterine leiomyomas treated with gonadotropin-releasing hormone agonist

OBJECTIVE: Our purpose was to investigate the histopathologic changes in uterine leiomyomas in cell proliferation, proliferating cell nuclear antigen expression, angiogenesis, and apoptosis after treatment with gonadotropin- releasing hormone agonist. STUDY DESIGN: Fifteen consecutive patients who had undergone gonadotropin-releasing hormone agonist treatment before surgery and 44 patients who did not were studied. The volumes of myomas were determined ultrasonographically, and in patients receiving gonadotropin-releasing hormone agonist therapy measurements were done again after administration of the gonadotropin-releasing hormone agonist to evaluate the response to treatment. Paraffin sections were stained with hematoxylin and eosin PC 10 for proliferating cell nuclear antigen expression. MIB 1 for measurement of cell proliferation, ApopTag for apoptosis, and factor VIII for quantitation of microvessel density. A deoxyribonucleic acid fragmentation test was also done on nine cases with available frozen tissues RESULTS: Most of the leiomyomas showed substantial express on of proliferating cell nuclear antigen Gonadotropin-releasing hormone agonist therapy further induced significant overexpression of proliferating cell nuclear antigen (p = 0.0004 χ² test. All three leiomyomas that failed to respond to therapy showed less proliferating cell nuclear antigen staining compared with the good responders. In contrast, data from MIB 1 immunostaining showed that <0.3% of leiomyoma cells were proliferating. However, positive-staining cells were more frequently detected in the treatment group (0.075% ± 0.091% vs 0.002% ± 0.010%, p = 0.0002 Mann-Whitney U test). Apoptosis developed spontaneously in leiomyoma cells independent of gonadotropin-releasing hormone agonist therapy. No significant change in apoptosis but a significant increase in microvessel density was observed in the treatment group compared with the control group. CONCLUSION: Enhanced deoxyribonucleic acid damage or repair with cell groWth arrest may be responsible for the action of gonadotropin- releasing hormone agonist in shrinking uterine leiomyomas. Moreover the extent of proliferating cell nuclear antigen expression seems to be associated with the response to gonadotropin-releasing hormone agonist therapy.