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Epithelial-to-mesenchymal transition in ameloblastoma: focus on morphologically evident mesenchymal phenotypic transition

The ameloblastoma is the most common and clinically significant odontogenic epithelial neoplasm known for its locally-invasive behaviour and high recurrence risk. Epithelial-to-mesenchymal transition (EMT) is a fundamental process whereby epithelial cells lose their epithelial characteristics and ga...

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Main Authors: Siar, Chong Huat, Ng, Kok Han
Format: Article
Published: Lippincott Williams & Wilkins 2019
Subjects:
R Medicine
RK Dentistry
Online Access:http://eprints.um.edu.my/23447/
https://doi.org/10.1016/j.pathol.2019.04.004
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spelling my.um.eprints.234472020-01-16T01:48:21Z http://eprints.um.edu.my/23447/ Epithelial-to-mesenchymal transition in ameloblastoma: focus on morphologically evident mesenchymal phenotypic transition Siar, Chong Huat Ng, Kok Han R Medicine RK Dentistry The ameloblastoma is the most common and clinically significant odontogenic epithelial neoplasm known for its locally-invasive behaviour and high recurrence risk. Epithelial-to-mesenchymal transition (EMT) is a fundamental process whereby epithelial cells lose their epithelial characteristics and gain mesenchymal properties. EMT induction via transcription repression has been investigated in ameloblastoma. However, morphologically evident mesenchymal phenotypic transition remains ill-defined. To determine this, 24 unicystic (UA), 34 solid/multicystic (SA) and 18 recurrent ameloblastoma (RA) were immunohistochemically examined for three EMT-related mesenchymal markers, alpha smooth muscle actin (α-SMA), osteonectin and neuronal cadherin (N-cadherin). All three factors were heterogeneously detected in ameloblastoma samples (α-SMA, n=71/76, 93.4%; osteonectin, n=72/76, 94.7%; N-cadherin, n=24/76, 31.6%). In the tumoural parenchyma, immunoreactive cells were not morphologically distinct from their non-reactive cellular counterparts. Rather, α-SMA and osteonectin predominantly labelled the cytoplasm of central polyhedral > peripheral columnar/cuboidal tumour cells. N-cadherin demonstrated weak-to-moderate circumferential membranous staining in both neoplastic cell types and cytoplasmic expression in spindle-celled epithelium of desmoplastic amelobastoma. For all tumour subsets, α-SMA and osteonectin scored significantly higher in the stroma > parenchyma whilst α-SMA was overexpressed along the tumour invasive front > centre (p<0.05). Stromal N-cadherin scored higher in SA > UA and RA > UA (p<0.05). Other clinicopathological parameters showed no significant associations. Taken together, acquisition of mesenchymal traits without morphologically evident mesenchymal alteration suggests partial EMT in ameloblastoma. Stromal upregulation of these proteins in SA and RA implicates a role in local invasiveness. © 2019 Royal College of Pathologists of Australasia Lippincott Williams & Wilkins 2019 Article PeerReviewed Siar, Chong Huat and Ng, Kok Han (2019) Epithelial-to-mesenchymal transition in ameloblastoma: focus on morphologically evident mesenchymal phenotypic transition. Pathology, 51 (5). pp. 494-501. ISSN 0031-3025 https://doi.org/10.1016/j.pathol.2019.04.004 doi:10.1016/j.pathol.2019.04.004
institution Universiti Malaya
building UM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaya
content_source UM Research Repository
url_provider http://eprints.um.edu.my/
topic R Medicine
RK Dentistry
spellingShingle R Medicine
RK Dentistry
Siar, Chong Huat
Ng, Kok Han
Epithelial-to-mesenchymal transition in ameloblastoma: focus on morphologically evident mesenchymal phenotypic transition
description The ameloblastoma is the most common and clinically significant odontogenic epithelial neoplasm known for its locally-invasive behaviour and high recurrence risk. Epithelial-to-mesenchymal transition (EMT) is a fundamental process whereby epithelial cells lose their epithelial characteristics and gain mesenchymal properties. EMT induction via transcription repression has been investigated in ameloblastoma. However, morphologically evident mesenchymal phenotypic transition remains ill-defined. To determine this, 24 unicystic (UA), 34 solid/multicystic (SA) and 18 recurrent ameloblastoma (RA) were immunohistochemically examined for three EMT-related mesenchymal markers, alpha smooth muscle actin (α-SMA), osteonectin and neuronal cadherin (N-cadherin). All three factors were heterogeneously detected in ameloblastoma samples (α-SMA, n=71/76, 93.4%; osteonectin, n=72/76, 94.7%; N-cadherin, n=24/76, 31.6%). In the tumoural parenchyma, immunoreactive cells were not morphologically distinct from their non-reactive cellular counterparts. Rather, α-SMA and osteonectin predominantly labelled the cytoplasm of central polyhedral > peripheral columnar/cuboidal tumour cells. N-cadherin demonstrated weak-to-moderate circumferential membranous staining in both neoplastic cell types and cytoplasmic expression in spindle-celled epithelium of desmoplastic amelobastoma. For all tumour subsets, α-SMA and osteonectin scored significantly higher in the stroma > parenchyma whilst α-SMA was overexpressed along the tumour invasive front > centre (p<0.05). Stromal N-cadherin scored higher in SA > UA and RA > UA (p<0.05). Other clinicopathological parameters showed no significant associations. Taken together, acquisition of mesenchymal traits without morphologically evident mesenchymal alteration suggests partial EMT in ameloblastoma. Stromal upregulation of these proteins in SA and RA implicates a role in local invasiveness. © 2019 Royal College of Pathologists of Australasia
format Article
author Siar, Chong Huat
Ng, Kok Han
author_facet Siar, Chong Huat
Ng, Kok Han
author_sort Siar, Chong Huat
title Epithelial-to-mesenchymal transition in ameloblastoma: focus on morphologically evident mesenchymal phenotypic transition
title_short Epithelial-to-mesenchymal transition in ameloblastoma: focus on morphologically evident mesenchymal phenotypic transition
title_full Epithelial-to-mesenchymal transition in ameloblastoma: focus on morphologically evident mesenchymal phenotypic transition
title_fullStr Epithelial-to-mesenchymal transition in ameloblastoma: focus on morphologically evident mesenchymal phenotypic transition
title_full_unstemmed Epithelial-to-mesenchymal transition in ameloblastoma: focus on morphologically evident mesenchymal phenotypic transition
title_sort epithelial-to-mesenchymal transition in ameloblastoma: focus on morphologically evident mesenchymal phenotypic transition
publisher Lippincott Williams & Wilkins
publishDate 2019
url http://eprints.um.edu.my/23447/
https://doi.org/10.1016/j.pathol.2019.04.004
_version_ 1657488211041058816
score 13.211869

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