Telocytes: Newly Discovered Interstitial Cells in the Human Female Internal Reproductive Organs – Identification of a Suitable Immunohistochemical Marker and Possible Significance in the Pathogenesis of Uterine Fibroids

Abstract

IntroductionTelocytes are a cell population discovered in 2005. Within the organs of the female reproductive system (FRS), telocytes were described as having an immunomodulatory role and also functioning as hormone sensors. From the pathological perspective, telocytes were described in the pathogenesis of a wide spectrum of different conditions, including a role in tumorigenesis. The gold standard of telocyte research is electron microscopy, but immunohistochemistry is also widely applied. The main objective was to identify the most suitable immunohistochemical marker and subsequently use it in the study of uterine specimens from patients with uterine fibroids (leiomyomas).Material andMethodsUterine specimens were obtained from 26 patients who underwent hysterectomy for various indications, including ectopic pregnancy and uterine fibroids. From all the uteruses, representative specimens were obtained from the myometrium and endometrium of the uterine body, and also from the endo‐ and exocervical mucosa. 5 μm thick sections were further processed for immunohistochemistry. To identify the most suitable marker of telocytes, 8 primary antibodies were used: CD117/c‐kit, CD34, vimentin, α‐smooth muscle actin, progesterone and estrogen receptor, desmin and S100 protein (DAKO, Denmark).ResultsThe most specific marker was c‐kit. C‐kit‐positive cells were spindle‐shaped, triangular and star‐shaped. C‐kit positive cells were located in the endometrium, myometrium, exocervical, and endocervical mucosa. Comparing the distribution within the individual parts of the uterus, the most numerous population was observed within the myometrium. A considerable number of telocytes was also observed within the endocervical mucosa, while the fewest telocytes were described in the endometrium and exocervical mucosa. In the specimens of uterine fibroids, the non‐affected parts of the myometrium contained c‐kit positive cells within all the myometrial sublayers. The average c‐kit positivity expressed in percentage was 2.19 ± 0.51%. Those parts of the myometrium affected by uterine fibroids displayed complete c‐kit negativity.ConclusionC‐kit is the most suitable marker in the research of telocytes in the FRS. The loss of telocytes in the myometrium may have a role in the pathogenesis of uterine fibroids via three mechanisms: 1) hormonal imbalance, 2) stem cell dysregulation and 3) diminished angiogenesis. Therefore, therapeutic targeting of telocytes can be a potential future approach in the treatment of this condition.