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862 Homologous recombination deficiency (HRD) in primary advanced stage and recurrent P53 abnormal endometrial carcinoma
  1. Suzana Mittelstadt1,2,
  2. Annette Staebler3,
  3. Christina Walter2,
  4. Carsten Denkert4,
  5. Katharina Knoll5,
  6. Alain Zeimet5,
  7. Stefan Kommoss1,2 and
  8. Marcel Philip Grube1,2
  1. 1Department of Obstetrics and Gynecology, Diakonie Klinikum Schwäbisch Hall, Schwäbisch Hall, Germany
  2. 2Department of Women's Health, Tübingen University Hospital, Tübingen, Germany
  3. 3Institute of Pathology and Neuropathology, Tübingen University Hospital, Tübingen, Germany
  4. 4Institute of Pathology, Marburg University, Marburg, Germany
  5. 5Department of Gynecology and Obstetrics, Medical University of Innsbruck, Innsbruck, Austria


Introduction/Background Endometrial carcinoma (EC) classify as p53 abnormal (p53abn) in up to 25% EC patients according to the current WHO classification. Despite the high sensitivity of p53abn EC to platinum-based chemotherapy, prognosis in this molecular group is poor. The combination of low mutational burden and high genomic instability is remarkably in this EC subpopulation and very similar to serous ovarian cancer, suggesting opportunities for overlapping treatment paradigms. Since p53 is part of several DNA repair pathways, p53 abnormality can lead to impaired homologous recombination deficiency(HRD), which can result in chromosomal instability and copy-number alterations. The aim of this study was to investigate HRD in primary advanced and recurrent p53abn EC patients.

Methodology Formalin-fixed paraffin-embedded tumor samples from patients with primary advanced stage (FIGO III/IV) or recurrent disease were submitted to molecular classification including p53 and mismatch repair protein immunohistochemistry as well as POLE mutation testing. In patients with p53abn molecular classification HRD-testing was performed using the Myriad myChoice CDx test.

Results A cohort of 53 patients was available for HRD testing, of which genomic instability scores (GIS) could be obtained in 37 cases. 28 patients (76%) were diagnosed with primary advanced stage disease, 9 patients (24%) were included with recurrent tumor after primary early stage (FIGO I/II) disease. Histology was serous in n=19 (51%), and endometrioid in n=10 cases (27%). According to ovarian carcinoma GIS cut-off values, n=8 (22%) patients were considered HRD positive (Figure 1), of which in 3 cases somatic BRCA mutation were found.

Conclusion A significant number of p53abn EC were found to be HRD positive in this serie. Further investigation of HRD and EC-specific GIS cut-off value are highly warranted and may help to improve outcome in this specific EC subgroup. Patients with p53abn tumors may benefit from PARP inhibition and HRD testing may provide key information for patient selection.

Disclosures This project was supported by GSK Pharmaceutical industry company.

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