Geburtshilfe Frauenheilkd 2014; 74 - PO_Onko01_01
DOI: 10.1055/s-0034-1388327

Synchronous stage IA endometrial and ovarian carcinomas share common mutations: implications for tumour evolution and clinical staging

M Maaßen 1, 2, M Anglesio 3, A Staebler 4, D Wallwiener 1, F Kommoss 5, M McConechy 3, A Karnezis 3, HL Chang 3, DG Huntsman 2, 3, CB Gilks 3, S Brucker 1, FA Taran 1, S Kommoss 1
  • 1Universitätsfrauenklinik, Tübingen, Germany
  • 2Center for Translational and Applied Genomics, Vancouver, Canada
  • 3Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, Canada
  • 4Universitätsklinikum, Institut für Pathologie, Tübingen, Germany
  • 5Synlab MVZ Pathologie, Mannheim, Germany

Introduction: Synchronous endometrial and ovarian carcinomas (SENOCA) are problematic due to a lack of objective criteria to define them as independent primary tumours or primary/metastasis pairs, a vital distinction for clinical staging and treatment. We sought to test whether these tumours have mutational profiles supporting independent or common origins.

Methods: We identified 17 endometrioid SENOCA classified as independent stage IA primary tumours. Genomic DNA was extracted from germline and tumour tissues and next-generation sequencing across 34 genes frequently mutated in endometrial and/or ovarian tumours was performed.

Results: All tumours classified as independent primaries shared many identical somatic mutations. Types of mutations (coding and non-coding) and number of mutations in common varied across pairs with mutations of POLE appearing to be the most commonly mutated gene between pairs. No tumour pairs in our dataset appeared to have exclusively distinct sets of mutations.

Conclusion: The shared mutations in SENOCA stage IA support a common origin. However, an overall excellent outcome for these tumours argues against a primary and metastasis model. We propose our data are consistent with tumours originating from a common precursor, such as endometriosis, that is able to colonize multiple distant sites and subsequently give rise to apparent low-stage independent synchronous tumours. These results have important implications for our understanding of tumour evolution and the utility of mutation testing in the classification, clinical staging and treatment of SENOCA. The knowledge gained here is important in understanding early transformation events and identification of “high-risk” from more common endometriosis.