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Tytuł pozycji:

Combined CCNE1 high‐level amplification and overexpression is associated with unfavourable outcome in tubo‐ovarian high‐grade serous carcinoma

Tytuł :
Combined CCNE1 high‐level amplification and overexpression is associated with unfavourable outcome in tubo‐ovarian high‐grade serous carcinoma
Autorzy :
Angela MY Chan
Emeka Enwere
John B McIntyre
Holly Wilson
Chidera Nwaroh
Nicholas Wiebe
Young Ou
Shuhong Liu
Katharina Wiedemeyer
Peter F Rambau
Xin Grevers
Donald G Morris
Paola Neri
C Blake Gilks
Frank Visser
Nhu Le
Li Luo
Linda S Cook
Martin Köbel
Pokaż więcej
Temat :
ovarian cancer
high grade serous carcinoma
CCNE1
cyclin E1
amplification
prognosis
Pathology
RB1-214
Źródło :
The Journal of Pathology: Clinical Research, Vol 6, Iss 4, Pp 252-262 (2020)
Wydawca :
Wiley, 2020.
Rok publikacji :
2020
Kolekcja :
LCC:Pathology
Typ dokumentu :
article
Opis pliku :
electronic resource
Język :
English
ISSN :
2056-4538
Relacje :
https://doaj.org/toc/2056-4538
DOI :
10.1002/cjp2.168
Dostęp URL :
https://doaj.org/article/6ee18146a012411aa9e07aebf83b2262
Numer akcesji :
edsdoj.6ee18146a012411aa9e07aebf83b2262
Czasopismo naukowe
Abstract CCNE1 amplification is a recurrent alteration associated with unfavourable outcome in tubo‐ovarian high‐grade serous carcinoma (HGSC). We aimed to investigate whether immunohistochemistry (IHC) can be used to identify CCNE1 amplification status and to validate whether CCNE1 high‐level amplification and overexpression are prognostic in HGSC. A testing set of 528 HGSC samples stained with two optimised IHC assays (clones EP126 and HE12) was subjected to digital image analysis and visual scoring. DNA and RNA chromogenic in situ hybridisation for CCNE1 were performed. IHC cut‐off was determined by receiver operating characteristics (ROC). Survival analyses (endpoint ovarian cancer specific survival) were performed and validated in an independent validation set of 764 HGSC. Finally, combined amplification/expression status was evaluated in cases with complete data (n = 1114). CCNE1 high‐level amplification was present in 11.2% of patients in the testing set and 10.2% in the combined cohort. The optimal cut‐off for IHC to predict CCNE1 high‐level amplification was 60% positive tumour cells with at least 5% strong staining cells (sensitivity 81.6%, specificity 77.4%). CCNE1 high‐level amplification and overexpression were associated with survival in the testing and validation set. Combined CCNE1 high‐level amplification and overexpression was present in 8.3% of patients, mutually exclusive to germline BRCA1/2 mutation and significantly associated with a higher risk of death in multivariate analysis adjusted for age, stage and cohort (hazard ratio = 1.78, 95 CI% 1.38–2.26, p

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