title: Linking uterine serous carcinoma to BRCA1/2-associated cancer syndrome: A meta-analysis and case report.
abstract: Uterine serous carcinoma (USC) shows greater morphological, clinical and molecular similarities to high-grade ovarian tubal serous carcinoma than to other types of endometrial cancer. As high-grade ovarian tubal serous carcinoma is known to be associated with BRCA1/2 pathogenic germline mutations (PMs), we aimed to explore whether USC is also a constituent of hereditary breast and ovarian cancer syndrome.
  
  
  
  Pubmed, EMBASE and Web of Science were searched in July 2016 for articles assessing the association between USC and germline BRCA1/2-PMs. Pooled analysis and comparisons were performed using a random effects logistic model, stratifying for ethnicity (Ashkenazi versus non-Ashkenazi). In addition, tumour tissue from an USC case with a hereditary BRCA1-PM was analysed for loss of heterozygosity at the BRCA1 locus and was functionally analysed for homologous recombination proficiency.
  
  
  
  The search yielded 1893 citations, 10 studies were included describing 345 USC patients. For Ashkenazi Jews, the pooled odds ratio of having a germline BRCA1/2-PM was increased in USC patients compared with the general Ashkenazi population: odds ratio 5.4 (95%confidence interval: 2.2-13.1). In the patient with USC, we identified the known germline BRCA1-PM in the tumour DNA. Furthermore, we showed both loss of heterozygosity of the wild-type allele and a deficiency of homologous recombination.
  
  
  
  This study suggests that USC may be an overlooked component of BRCA1/2-associated hereditary breast and ovarian cancer syndrome. Screening for germline BRCA1/2-PMs should be considered in patients diagnosed with USC, especially in cases with a positive first-degree family history for breast and/or ovarian cancer.
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: M M
authors.initials: MM
authors.lastname: de Jonge
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: A L
authors.initials: AL
authors.lastname: Mooyaart
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: M P G
authors.initials: MP
authors.lastname: Vreeswijk
authors.affiliation: Department of Gynecology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: C D
authors.initials: CD
authors.lastname: de Kroon
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: van Wezel
authors.affiliation: Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: C J
authors.initials: CJ
authors.lastname: van Asperen
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: V T H B M
authors.initials: VT
authors.lastname: Smit
authors.affiliation: Department of Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: O M
authors.initials: OM
authors.lastname: Dekkers
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: t.bosse@lumc.nl.
authors.forename: T
authors.initials: T
authors.lastname: Bosse
mesh_terms: D002277:Carcinoma / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D014594:Uterine Neoplasms / Q000235:genetics*
keywords: BRCA1; BRCA2; Germline mutation; Meta-analysis; Uterine serous carcinoma