Cellular senescence in usual type uterine leiomyoma

Objective: To evaluate the role of senescence in symptomatic patients with multifibroids. Design: A cohort study. Setting: University research laboratory. Patient(s): Eighty-six fibroids collected from 14 patients who underwent myomectomy or hysterectomy. Intervention(s): Senescence-associated β-galactosidase (SA-β-Gal) stain in fresh-frozen tissue; reverse-transcription polymerase chain reaction (RT-PCR); MicroRNA in situ hybridization (MISH); immunohistochemistry in formalin-fixed paraffin-embedded tissue. Main Outcome Measure(s): Senescence measured by percentage of SA-β-Gal-positive cells; levels of let-7 microRNAs measured by RT-PCR and MISH; expression of p16^INK4a, Ki-67, HMGA1, and HMGA2 scaled by immunoreactivity. Result(s): About 58% (48 of 82) of tumors showed significant senescent change (SA-β-Gal positive) in >10% of the tumor volume. The overall trend was a higher level of senescence in small fibroids and older-aged women. Senescent fibroids were additionally shown to have, high levels of let-7 c, d, and f-2 and a low Ki-67 index. Conclusion(s): Senescence is a common cellular change in a large proportion of usual type fibroids. Similarly, senescence may explain the variation in growth rates of these tumors, and may prove to be an important molecular and cellular target in prevention of fibroid growth.