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The status of epidermal growth factor receptor in borderline ovarian tumours

The majority of borderline ovarian tumours (BOTs) behave in a benign fashion, but some may show aggressive behavior. The reason behind this has not been elucidated. The epidermal growth factor receptor (EGFR) is known to contribute to cell survival signals as well as metastatic potential of some tum...

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Autores principales: Showeil, Rania, Romano, Claudia, Valganon, Mikel, Lambros, Maryou, Trivedi, Pritesh, Van Noorden, Susan, Sriraksa, Ruethairat, El-Kaffash, Dalal, El-Etreby, Nour, Natrajan, Rachael, Foroni, Letizia, Osborne, Richard, El-Bahrawy, Mona
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4891141/
https://www.ncbi.nlm.nih.gov/pubmed/26870997
http://dx.doi.org/10.18632/oncotarget.7257
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author Showeil, Rania
Romano, Claudia
Valganon, Mikel
Lambros, Maryou
Trivedi, Pritesh
Van Noorden, Susan
Sriraksa, Ruethairat
El-Kaffash, Dalal
El-Etreby, Nour
Natrajan, Rachael
Foroni, Letizia
Osborne, Richard
El-Bahrawy, Mona
author_facet Showeil, Rania
Romano, Claudia
Valganon, Mikel
Lambros, Maryou
Trivedi, Pritesh
Van Noorden, Susan
Sriraksa, Ruethairat
El-Kaffash, Dalal
El-Etreby, Nour
Natrajan, Rachael
Foroni, Letizia
Osborne, Richard
El-Bahrawy, Mona
author_sort Showeil, Rania
collection PubMed
description The majority of borderline ovarian tumours (BOTs) behave in a benign fashion, but some may show aggressive behavior. The reason behind this has not been elucidated. The epidermal growth factor receptor (EGFR) is known to contribute to cell survival signals as well as metastatic potential of some tumours. EGFR expression and gene status have not been thoroughly investigated in BOTs as it has in ovarian carcinomas. In this study we explore protein expression as well as gene mutations and amplifications of EGFR in BOTs in comparison to a subset of other epithelial ovarian tumours. We studied 85 tumours, including 61 BOTs, 10 low grade serous carcinomas (LGSCs), 9 high grade serous carcinomas (HGSCs) and 5 benign epithelial tumours. EGFR protein expression was studied using immunohistochemistry. Mutations were investigated by Sanger sequencing exons 18-21 of the tyrosine kinase domain of EGFR. Cases with comparatively higher protein expression were examined for gene amplification by chromogenic in situ hybridization. We also studied the tumours for KRAS and BRAF mutations. Immunohistochemistry results revealed both cytoplasmic and nuclear EGFR expression with variable degrees between tumours. The level of nuclear localization was relatively higher in BOTs and LGSCs as compared to HGSCs or benign tumours. The degree of nuclear expression of BOTs showed no significant difference from that in LGSCs (mean ranks 36.48, 33.05, respectively, p=0.625), but was significantly higher than in HGSCs (mean ranks: 38.88, 12.61 respectively, p< 0.001) and benign tumours (mean ranks: 35.18, 13.00 respectively, p= 0.010). Cytoplasmic expression level was higher in LGSCs. No EGFR gene mutations or amplification were identified, yet different polymorphisms were detected. Five different types of point mutations in the KRAS gene and the V600E BRAF mutation were detected exclusively in BOTs and LGSCs. Our study reports for the first time nuclear localization of EGFR in BOTs. The nuclear localization similarities between BOTs and LGSCs and not HGSCs support the hypothesis suggesting evolution of LGSCs from BOTs. We also confirm that EGFR mutations and amplifications are not molecular events in the pathogenesis of BOTs.
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spelling pubmed-48911412016-06-23 The status of epidermal growth factor receptor in borderline ovarian tumours Showeil, Rania Romano, Claudia Valganon, Mikel Lambros, Maryou Trivedi, Pritesh Van Noorden, Susan Sriraksa, Ruethairat El-Kaffash, Dalal El-Etreby, Nour Natrajan, Rachael Foroni, Letizia Osborne, Richard El-Bahrawy, Mona Oncotarget Research Paper The majority of borderline ovarian tumours (BOTs) behave in a benign fashion, but some may show aggressive behavior. The reason behind this has not been elucidated. The epidermal growth factor receptor (EGFR) is known to contribute to cell survival signals as well as metastatic potential of some tumours. EGFR expression and gene status have not been thoroughly investigated in BOTs as it has in ovarian carcinomas. In this study we explore protein expression as well as gene mutations and amplifications of EGFR in BOTs in comparison to a subset of other epithelial ovarian tumours. We studied 85 tumours, including 61 BOTs, 10 low grade serous carcinomas (LGSCs), 9 high grade serous carcinomas (HGSCs) and 5 benign epithelial tumours. EGFR protein expression was studied using immunohistochemistry. Mutations were investigated by Sanger sequencing exons 18-21 of the tyrosine kinase domain of EGFR. Cases with comparatively higher protein expression were examined for gene amplification by chromogenic in situ hybridization. We also studied the tumours for KRAS and BRAF mutations. Immunohistochemistry results revealed both cytoplasmic and nuclear EGFR expression with variable degrees between tumours. The level of nuclear localization was relatively higher in BOTs and LGSCs as compared to HGSCs or benign tumours. The degree of nuclear expression of BOTs showed no significant difference from that in LGSCs (mean ranks 36.48, 33.05, respectively, p=0.625), but was significantly higher than in HGSCs (mean ranks: 38.88, 12.61 respectively, p< 0.001) and benign tumours (mean ranks: 35.18, 13.00 respectively, p= 0.010). Cytoplasmic expression level was higher in LGSCs. No EGFR gene mutations or amplification were identified, yet different polymorphisms were detected. Five different types of point mutations in the KRAS gene and the V600E BRAF mutation were detected exclusively in BOTs and LGSCs. Our study reports for the first time nuclear localization of EGFR in BOTs. The nuclear localization similarities between BOTs and LGSCs and not HGSCs support the hypothesis suggesting evolution of LGSCs from BOTs. We also confirm that EGFR mutations and amplifications are not molecular events in the pathogenesis of BOTs. Impact Journals LLC 2016-02-08 /pmc/articles/PMC4891141/ /pubmed/26870997 http://dx.doi.org/10.18632/oncotarget.7257 Text en Copyright: © 2016 Showeil et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Showeil, Rania
Romano, Claudia
Valganon, Mikel
Lambros, Maryou
Trivedi, Pritesh
Van Noorden, Susan
Sriraksa, Ruethairat
El-Kaffash, Dalal
El-Etreby, Nour
Natrajan, Rachael
Foroni, Letizia
Osborne, Richard
El-Bahrawy, Mona
The status of epidermal growth factor receptor in borderline ovarian tumours
title The status of epidermal growth factor receptor in borderline ovarian tumours
title_full The status of epidermal growth factor receptor in borderline ovarian tumours
title_fullStr The status of epidermal growth factor receptor in borderline ovarian tumours
title_full_unstemmed The status of epidermal growth factor receptor in borderline ovarian tumours
title_short The status of epidermal growth factor receptor in borderline ovarian tumours
title_sort status of epidermal growth factor receptor in borderline ovarian tumours
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4891141/
https://www.ncbi.nlm.nih.gov/pubmed/26870997
http://dx.doi.org/10.18632/oncotarget.7257
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