TY - JOUR
T1 - Characterization of Primary Cilia in Normal Fallopian Tube Epithelium and Serous Tubal Intraepithelial Carcinoma
AU - Abdelhamed, Zakia A.
AU - Ryan, Thomas A.
AU - Fuller, Martin
AU - Coulson-Gilmer, Camilla
AU - Abdelmottaleb, Dina I.
AU - Wang, Tian Li
AU - Kaun, Jen Chun
AU - Wang, Peiyi
AU - Hutson, Richard
AU - Wilkinson, Nafisa
AU - Bell, Sandra M.
AU - Johnson, Colin A.
N1 - Funding Information:
This work was supported by European Commission FP7 (Seventh Framework Programme for Research) grant number 241955 (SYSCILIA) and MRC project grant (MR/M000532/1) to C.A.J., a Rosetree’s Trust fellowship (M279) to Z.A.A., and a Rosetree’s Trust project grant (M279-F1) to C.A.J. and S.M.B., C.C.G. was supported by a Cancer Research UK studentship. The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of IGCS and ESGO.
PY - 2018/10
Y1 - 2018/10
N2 - 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.
AB - 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.
KW - Dynein axonemal heavy chain 5
KW - Fallopian tube
KW - Primary cilia
KW - Serous tubal intraepithelial carcinoma
KW - Smoothened
KW - Sonic Hedgehog signaling
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U2 - 10.1097/IGC.0000000000001321
DO - 10.1097/IGC.0000000000001321
M3 - Article
C2 - 30095490
AN - SCOPUS:85054889796
SN - 1048-891X
VL - 28
SP - 1535
EP - 1544
JO - International Journal of Gynecological Cancer
JF - International Journal of Gynecological Cancer
IS - 8
ER -