title: Tracking the origin of simultaneous endometrial and ovarian cancer by next-generation sequencing - a case report.
abstract: Endometrioid adenocarcinoma of the uterus and ovarian endometrioid carcinoma share many morphological and molecular features. Differentiation between simultaneous primary carcinomas and ovarian metastases of an endometrial cancer may be very challenging but is essential for prognostic and therapeutic considerations.
  
  
  
  In the present case study of a 33 year-old patient we used targeted amplicon next-generation re-sequencing for clarifying the origin of synchronous endometrioid cancer of the corpus uteri and the left ovary. The patient developed a metachronous lung metastasis of an endometrioid adenocarcinoma four years after hyster- and adnexectomy, vaginal brachytherapy and treatment with the synthetic steroid tibolone. Removal of the metastasis and megestrol treatment for seven years led to a complete remission. A total of 409 genes from the Ampliseq Comprehensive Cancer Panel (Ion Torrent, Thermo Fisher) were analysed by next generation sequencing and mutations in 10 genes, including ARID1A, CTNNB1, PIK3CA and PTEN were identified and confirmed by Sanger sequencing. Primary endometrial as well as ovarian cancer showed an identical mutational profile, suggesting the presence of an ovarian metastasis of the endometrial cancer, rather than a simultaneous endometrial and ovarian cancer. The metachronous lung metastasis showed a different mutational profile compared to the primary cancer. Immunohistochemical staining of the corresponding proteins suggested that the tumour development was driven by alterations in the protein function rather than by changes of the protein abundance in the cell.
  
  
  
  Our results have demonstrated next generation sequencing as a valuable tool in the differentiation of synchronous primary tumours and metastases, which has an important impact on the clinical decision making process. Similar to breast cancer, targeted therapies based on mutational tumour profiling will become increasingly important in endometrial and ovarian cancer. In summary, our results support the usage of next generation sequencing as a supplementary diagnostic tool, assisting in personalized precision medicine.
authors.affiliation: Institute of Pathology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Nadejda
authors.initials: N
authors.lastname: Valtcheva
authors.affiliation: Department of Gynaecology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Franziska M
authors.initials: FM
authors.lastname: Lang
authors.affiliation: Institute of Pathology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Aurelia
authors.initials: A
authors.lastname: Noske
authors.affiliation: Department of Gynaecology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Eleftherios P
authors.initials: EP
authors.lastname: Samartzis
authors.affiliation: Department of Gynaecology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Schmidt
authors.affiliation: Institute of Pathology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Elisa
authors.initials: E
authors.lastname: Bellini
authors.affiliation: Department of Gynaecology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Fink
authors.affiliation: Institute of Pathology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Holger
authors.initials: H
authors.lastname: Moch
authors.affiliation: Institute of Pathology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Markus
authors.initials: M
authors.lastname: Rechsteiner
authors.affiliation: Department of Gynaecology, University Hospital Zurich, Zurich, Switzerland. konstantin.dedes@usz.ch.
authors.forename: Konstantin J
authors.initials: KJ
authors.lastname: Dedes
authors.affiliation: Institute of Pathology, University Hospital Zurich, Zurich, Switzerland. peter.wild@usz.ch.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Wild
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D004252:DNA Mutational Analysis; D016889:Endometrial Neoplasms / Q000235:genetics / Q000473:pathology*; D005260:Female; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000556:secondary*; D009154:Mutation / Q000235:genetics*; D009378:Neoplasms, Multiple Primary / Q000235:genetics / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000556:secondary*; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor
keywords: Case report; Endometrial cancer; Metastasis; Next-generation sequencing; Ovarian cancer