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

Autor: Shuhong Liu, Holly E Wilson, John B. McIntyre, Paola Neri, Young Ou, Chidera Nwaroh, C. Blake Gilks, Donald Morris, Martin Köbel, Li Luo, Frank Visser, Emeka K. Enwere, Peter F Rambau, Katharina Wiedemeyer, Xin Grevers, Linda S. Cook, Nicholas Wiebe, Nhu D. Le, Angela My Chan
Rok vydání: 2020
Předmět:
Oncology
Serous carcinoma
amplification
Alberta
Risk Factors
cyclin E1
Predictive testing
In Situ Hybridization
Oncogene Proteins
Ovarian Neoplasms
Predictive marker
BRCA1 Protein
Hazard ratio
CCNE1
Immunohistochemistry
Gene Expression Regulation
Neoplastic
ovarian cancer
PARP inhibitor
Original Article
Female
lcsh:RB1-214
medicine.medical_specialty
Risk Assessment
Pathology and Forensic Medicine
Germline mutation
Predictive Value of Tests
Internal medicine
high grade serous carcinoma
Cyclin E
lcsh:Pathology
Biomarkers
Tumor
medicine
Animals
Humans
Germ-Line Mutation
BRCA2 Protein
British Columbia
business.industry
Carcinoma
Gene Amplification
Reproducibility of Results
Original Articles
medicine.disease
prognosis
Neoplasm Grading
Neoplasms
Cystic
Mucinous
and Serous
business
Ovarian cancer
Zdroj: The Journal of Pathology: Clinical Research
The Journal of Pathology: Clinical Research, Vol 6, Iss 4, Pp 252-262 (2020)
ISSN: 2056-4538
DOI: 10.1002/cjp2.168
Popis: 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
Databáze: OpenAIRE
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