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BRAF(V600E)-mutated ovarian serous borderline tumors are at relatively low risk for progression to serous carcinoma

Ovarian serous borderline tumor (SBT) is a known precursor of low-grade serous carcinoma. While most SBTs are cured surgically, some progress to carcinoma and a risk predictor for malignant relapse is needed to ensure vigilant follow-up and additional treatment. Activating mutations in KRAS or BRAF...

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Autores principales: Chui, M. Herman, Kjaer, Susanne K., Frederiksen, Kirsten, Hannibal, Charlotte G., Wang, Tian-Li, Vang, Russell, Shih, Ie-Ming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6901340/
https://www.ncbi.nlm.nih.gov/pubmed/31839880
http://dx.doi.org/10.18632/oncotarget.27326
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author Chui, M. Herman
Kjaer, Susanne K.
Frederiksen, Kirsten
Hannibal, Charlotte G.
Wang, Tian-Li
Vang, Russell
Shih, Ie-Ming
author_facet Chui, M. Herman
Kjaer, Susanne K.
Frederiksen, Kirsten
Hannibal, Charlotte G.
Wang, Tian-Li
Vang, Russell
Shih, Ie-Ming
author_sort Chui, M. Herman
collection PubMed
description Ovarian serous borderline tumor (SBT) is a known precursor of low-grade serous carcinoma. While most SBTs are cured surgically, some progress to carcinoma and a risk predictor for malignant relapse is needed to ensure vigilant follow-up and additional treatment. Activating mutations in KRAS or BRAF are present in around 60% of SBTs, but their relative impact on progression is unclear. We performed mutational analysis of KRAS and BRAF on 201 SBTs identified from a longitudinal cohort of SBTs after centralized pathology review. Compared to wildtype and KRAS-mutated SBTs, BRAF-mutated group of SBTs were less likely to exhibit micropapillary variant histology (p < 0.0001), were more frequently Stage I (p = 0.0023) and had a lower prevalence of associated endosalpingiosis (p = 0.0069). The histologic feature of diffuse presence of tumor cells with dense eosinophilic cytoplasm, while significantly associated with the BRAF(V600E) mutation (p < 0.0001), is 62% sensitive and 93% specific in identifying tumors with this mutation. After adjusting for age and stage, the risk of subsequent serous carcinoma was lower for SBTs harboring BRAF (HR 0.27, 95% CI 0.08–0.93), but not KRAS (HR 1.00, 95% CI 0.45–2.23) mutations, in comparison to wildtype SBTs. This study establishes the potential utility of mutation testing for guiding clinical management of ovarian SBT and underscores the importance of accurate morphologic distinction of micropapillary SBT from SBT with eosinophilic tumor cells, given their disparate prognostic implications.
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spelling pubmed-69013402019-12-13 BRAF(V600E)-mutated ovarian serous borderline tumors are at relatively low risk for progression to serous carcinoma Chui, M. Herman Kjaer, Susanne K. Frederiksen, Kirsten Hannibal, Charlotte G. Wang, Tian-Li Vang, Russell Shih, Ie-Ming Oncotarget Research Paper Ovarian serous borderline tumor (SBT) is a known precursor of low-grade serous carcinoma. While most SBTs are cured surgically, some progress to carcinoma and a risk predictor for malignant relapse is needed to ensure vigilant follow-up and additional treatment. Activating mutations in KRAS or BRAF are present in around 60% of SBTs, but their relative impact on progression is unclear. We performed mutational analysis of KRAS and BRAF on 201 SBTs identified from a longitudinal cohort of SBTs after centralized pathology review. Compared to wildtype and KRAS-mutated SBTs, BRAF-mutated group of SBTs were less likely to exhibit micropapillary variant histology (p < 0.0001), were more frequently Stage I (p = 0.0023) and had a lower prevalence of associated endosalpingiosis (p = 0.0069). The histologic feature of diffuse presence of tumor cells with dense eosinophilic cytoplasm, while significantly associated with the BRAF(V600E) mutation (p < 0.0001), is 62% sensitive and 93% specific in identifying tumors with this mutation. After adjusting for age and stage, the risk of subsequent serous carcinoma was lower for SBTs harboring BRAF (HR 0.27, 95% CI 0.08–0.93), but not KRAS (HR 1.00, 95% CI 0.45–2.23) mutations, in comparison to wildtype SBTs. This study establishes the potential utility of mutation testing for guiding clinical management of ovarian SBT and underscores the importance of accurate morphologic distinction of micropapillary SBT from SBT with eosinophilic tumor cells, given their disparate prognostic implications. Impact Journals LLC 2019-12-03 /pmc/articles/PMC6901340/ /pubmed/31839880 http://dx.doi.org/10.18632/oncotarget.27326 Text en Copyright: © 2019 Chui et al. https://creativecommons.org/licenses/by/3.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Chui, M. Herman
Kjaer, Susanne K.
Frederiksen, Kirsten
Hannibal, Charlotte G.
Wang, Tian-Li
Vang, Russell
Shih, Ie-Ming
BRAF(V600E)-mutated ovarian serous borderline tumors are at relatively low risk for progression to serous carcinoma
title BRAF(V600E)-mutated ovarian serous borderline tumors are at relatively low risk for progression to serous carcinoma
title_full BRAF(V600E)-mutated ovarian serous borderline tumors are at relatively low risk for progression to serous carcinoma
title_fullStr BRAF(V600E)-mutated ovarian serous borderline tumors are at relatively low risk for progression to serous carcinoma
title_full_unstemmed BRAF(V600E)-mutated ovarian serous borderline tumors are at relatively low risk for progression to serous carcinoma
title_short BRAF(V600E)-mutated ovarian serous borderline tumors are at relatively low risk for progression to serous carcinoma
title_sort braf(v600e)-mutated ovarian serous borderline tumors are at relatively low risk for progression to serous carcinoma
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6901340/
https://www.ncbi.nlm.nih.gov/pubmed/31839880
http://dx.doi.org/10.18632/oncotarget.27326
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