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Characterization of primary cilia in normal fallopian tube epithelium and serous tubal intraepithelial carcinoma

Characterization of primary cilia in normal fallopian tube epithelium and serous tubal intraepithelial carcinoma
Characterization of primary cilia in normal fallopian tube epithelium and serous tubal intraepithelial carcinoma
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.
1535-1544
Abdelhamed, Zakia
b5a01b20-6b33-40da-b24e-405f3c152906
Ryan, Thomas
ea35c378-0f6e-4ea0-8a55-2a8703d85412
Fuller, Martin
886bfc7f-cb30-4c18-b2b2-6ea34e5693f0
Coulson-Gilmer, Camilla
8979eb36-8916-4066-9c43-bdd638d89cb9
Abdelmottableb, Dina I.
2bce63c9-5e2c-4a11-b838-f3787dc8f146
Wang, Tian-Li
f0b00505-d321-4665-b57c-ac148b9f975f
Kaun, Jen-Chun
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Wang, Peiyi
5ebab5f5-71b7-4882-8320-d79c7312a97d
Hutson, Richard
6464169f-21df-4227-9ce6-e78c45a3a2eb
Wilkinson, Nafisa
2f818916-ed3d-4dad-b4b4-11e5257a85a0
Bell, Sandra M.
8af15e68-d66a-4d67-851a-baaad4fb91b8
Johnson, Colin
c0241c43-aa34-4f6f-a07b-4e5884968d73
Abdelhamed, Zakia
b5a01b20-6b33-40da-b24e-405f3c152906
Ryan, Thomas
ea35c378-0f6e-4ea0-8a55-2a8703d85412
Fuller, Martin
886bfc7f-cb30-4c18-b2b2-6ea34e5693f0
Coulson-Gilmer, Camilla
8979eb36-8916-4066-9c43-bdd638d89cb9
Abdelmottableb, Dina I.
2bce63c9-5e2c-4a11-b838-f3787dc8f146
Wang, Tian-Li
f0b00505-d321-4665-b57c-ac148b9f975f
Kaun, Jen-Chun
0dc9e651-4869-4492-884f-05c5d2631d92
Wang, Peiyi
5ebab5f5-71b7-4882-8320-d79c7312a97d
Hutson, Richard
6464169f-21df-4227-9ce6-e78c45a3a2eb
Wilkinson, Nafisa
2f818916-ed3d-4dad-b4b4-11e5257a85a0
Bell, Sandra M.
8af15e68-d66a-4d67-851a-baaad4fb91b8
Johnson, Colin
c0241c43-aa34-4f6f-a07b-4e5884968d73

Abdelhamed, Zakia, Ryan, Thomas, Fuller, Martin, Coulson-Gilmer, Camilla, Abdelmottableb, Dina I., Wang, Tian-Li, Kaun, Jen-Chun, Wang, Peiyi, Hutson, Richard, Wilkinson, Nafisa, Bell, Sandra M. and Johnson, Colin (2018) Characterization of primary cilia in normal fallopian tube epithelium and serous tubal intraepithelial carcinoma. International Journal of Gynecological Cancer, 28 (8), 1535-1544. (doi:10.1097/IGC.0000000000001321).

Record type: Article

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.

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Accepted/In Press date: 3 June 2018
e-pub ahead of print date: 1 October 2018
Published date: October 2018

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Local EPrints ID: 425908
URI: http://eprints.soton.ac.uk/id/eprint/425908
PURE UUID: ebe5fad2-4563-4f3a-b468-a1219a266daf

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Date deposited: 06 Nov 2018 17:30
Last modified: 15 Mar 2024 22:27

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Contributors

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

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