Characterization of Primary Cilia in Normal Fallopian Tube Epithelium and Serous Tubal Intraepithelial Carcinoma

Zakia A. Abdelhamed, Thomas A. Ryan, Martin Fuller, Camilla Coulson-Gilmer, Dina I. Abdelmottaleb, Tian Li Wang, Jen Chun Kaun, Peiyi Wang, Richard Hutson, Nafisa Wilkinson, Sandra M. Bell, Colin A. Johnson

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives The aim of this study was to investigate the distribution of primary cilia on secretory cells in normal fallopian tube (FT) and serous tubal intraepithelial carcinoma (STIC). Methods Fallopian tube tissue samples were obtained from 4 females undergoing prophylactic hysterectomies and 6 patients diagnosed with STIC. A mogp-TAg transgenic mouse STIC sample was also compared with a wild-type mouse FT sample. Serous tubal intraepithelial carcinoma was identified by hematoxylin and eosin staining and confirmed by positive Ki-67 and p53 immunohistochemical staining of tissue sections. We assessed the relative distribution of primary cilia on secretory cells and motile cilia on multiple ciliated cells by immunofluorescence and immunohistochemical staining. Ciliary function was assessed by immunofluorescence staining of specific ciliary marker proteins and responsiveness to Sonic Hedgehog signaling. Results Primary cilia are widespread on secretory cells in the ampulla, isthmus, and in particular, the fimbriae of human FT where they may appear to mediate ciliary-mediated Sonic Hedgehog signaling. A statistically significant reduction in the number of primary cilia on secretory cells was observed in human STIC samples compared with normal controls (P < 0.0002, Student t test), supported by similar findings in a mouse STIC sample. Immunohistochemical staining for dynein axonemal heavy chain 5 discriminated multiple motile cilia from primary cilia in human FT. Conclusions Primary cilia are widespread on secretory cells in the ampulla, isthmus, and in particular, the fimbriae of the human FT but are significantly reduced in both human and mouse STIC samples. Immunohistochemical staining for ciliary proteins may have clinical utility for early detection of STIC.

Original languageEnglish (US)
Pages (from-to)1535-1544
Number of pages10
JournalInternational Journal of Gynecological Cancer
Volume28
Issue number8
DOIs
StatePublished - Oct 2018

Keywords

  • Dynein axonemal heavy chain 5
  • Fallopian tube
  • Primary cilia
  • Serous tubal intraepithelial carcinoma
  • Smoothened
  • Sonic Hedgehog signaling

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

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