ArticleAnnals of oncology : official journal of the European Society for Medical Oncology2014
The performance of BRCA1 immunohistochemistry for detecting germline, somatic, and epigenetic BRCA1 loss in high-grade serous ovarian cancer.
Article in Annals of oncology : official journal of the European Society for Medical Oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- BRCA1 Expression by Immunohistochemistry and Prognosis in Ovarian Cancer: A Systematic Review and Meta-Analysis.Targeted oncology · 2020Pooled it
- PAK1 inhibition synergistically enhances the anti-tumor efficacy of PARP inhibitors in ovarian cancers.Genes & diseases · 2026Article
- BRCA1 Promoter Methylation in Ovarian Cancer: Clinical Relevance and a Novel Diagnostic Approach Using Fragment Analysis.Cancer science · 2025Article
- Type I or Type II Endometrial Carcinoma? Role of BRCA1 Immunohistochemistry.Asian Pacific journal of cancer prevention : APJCP · 2024Article
- Article
- Loss of BRCA1 expression and morphological features associated with BRCA1 promoter methylation status in triple-negative breast cancer.Journal of human genetics · 2021Article
- Immunohistochemical Biomarkers as a Surrogate of Molecular Analysis in Ovarian Carcinomas: A Review of the Literature.Diagnostics (Basel, Switzerland) · 2021Review
- Prognostic Relevance of BRCA1 Expression in Survival of Patients With Cervical Cancer.Frontiers in oncology · 2021Article
- Article
- Review
- Article
- Pathology of Hereditary Breast and Ovarian Cancer.Frontiers in oncology · 2020Article
- Impact of germline and somatic BRCA1/2 mutations: tumor spectrum and detection platforms.Gene therapy · 2017Review
- [Hereditary breast and ovarian cancer].Der Pathologe · 2017Review
- Androgen receptor expression predicts different clinical outcomes for breast cancer patients stratified by hormone receptor status.Oncotarget · 2016Article
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundBRCA1 expression can be lost by a variety of mechanisms including germline or somatic mutation and promotor hypermethylation. Given the potential importance of BRCA1 loss as a predictive and prognostic biomarker in high-grade serous ovarian cancer, we sought to evaluate the utility of BRCA1 immunohistochemistry (IHC) in screening for BRCA1 loss by germline, somatic, and epigenetic mechanisms. PATIENTS AND
methodsPatients with advanced high-grade serous ovarian cancer who had previously undergone germline BRCA1 testing were identified. Samples from each tumor were stained for BRCA1 and reviewed independently by two pathologists blinded to BRCA status. Tumors with abnormal BRCA1 IHC and wild-type germline testing underwent further evaluation for somatic BRCA1 mutations and promoter hypermethylation. McNemar's test was used to determine the association of BRCA1 IHC with germline BRCA1 mutations and BRCA1 loss through any mechanism. Kaplan-Meier methods were used to estimate overall survival (OS), and the log-rank test was used to assess differences between groups.
resultsInter-rater reliability between the two pathologists on BRCA IHC interpretation was very good (kappa coefficient 0.865, P = 0.16; McNemar's test). BRCA1 IHC was abnormal in 36% (48/135) of cases. When compared with germline BRCA1 status, BRCA1 IHC had a high negative predictive value (95.4%) but a low positive predictive value (PPV, 52.1%). When accounting for promoter hypermethylation and somatic mutations as alternative methods of BRCA1 loss, the PPV rose to 87.5%. Five-year OS rate was 49.6% [95% confidence interval (CI) 26.3% to 69.3%] for patients with germline BRCA1 mutations, 50.4% (95% CI 27.5% to 69.5%) for germline wild-type BRCA1 and abnormal IHC, and 52.1% (95% CI 38.4% to 64.2%) for germline wild-type BRCA1 and normal IHC (P = 0.92).
conclusionsBRCA1 IHC interpretation was a highly reproducible and accurate modality for detecting germline, somatic, or epigenetic mechanisms of BRCA1 loss. These results support further development of BRCA1 IHC as a potential biomarker for BRCA1 loss in high-grade serous ovarian cancer.
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