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417 Does serous tubal intraepithelial carcinoma metastasize? The clonal relationship between serous tubal intraepithelial carcinoma and subsequent high-grade serous carcinoma in BRCA1/2 germline pathogenic varient carriers several years after risk-reducing salpingo-ophorectomy
  1. Caroline BVan Den Berg1,
  2. Shatavisha Dasgupta2,3,
  3. Patricia C Ewing-Graham4,
  4. Jos Bart5,
  5. Hans J Bulten6,
  6. Katja N Gaarenstroom7,
  7. Joanne De Hullu8,
  8. Constantijne H Mom9,
  9. Marian JE Mourits10,
  10. Miranda Steenbeek8,
  11. Ronald Van Marion2 and
  12. Heleen JVan Beekhuizen1
  1. 1Department of Gynaecologic Oncology, Erasmus MC Cancer Center, University Medical Centre, Rotterdam, The Netherlands
  2. 2Department of Pathology, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands
  3. 3Imaging Platform, Broad Institute of MIT and Harvard, Cambridge, USA
  4. 4Department of Pathology, Erasmus MC Cancer Center, University Medical Centre, Rotterdam, The Netherlands
  5. 5Department of Pathology, University Medical Center, Groningen, The Netherlands
  6. 6Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands
  7. 7Department of Gynaecologic Oncology, Leiden University Medical Center, Leiden, The Netherlands
  8. 8Department of Gynaecologic Oncology, Radboud University Medical Center, Nijmegen, The Netherlands
  9. 9Center for Gynaecologic Oncology Amsterdam, Amsterdam University Medical Center, Amsterdam, The Netherlands
  10. 10Department of Gynaecologic Oncology, University of Groningen, Groningen, The Netherlands


Introduction/Background The majority of high-grade serous carcinomas (HGSCs) of the ovary, fallopian tube, and peritoneum arise from a precursor lesion called serous tubal intraepithelial carcinoma (STIC). It has been postulated that cells from STICs exfoliate into the peritoneal cavity and may later give rise to peritoneal HGSC. While co-existent STICs and HGSCs have been reported to share similar mutational profiles, the clonal relationship between temporally distant STICs and HGSCs have been infrequently studied and the natural history of STICs remains poorly understood.

Methodology We performed targeted searches in two national databases and identified a series of BRCA1/2 germline pathogenic variant (GPV) carriers (n=7) with isolated STIC at the time of their risk-reducing salpingo-ophorectomy (RRSO), who later developed HGSC. We investigated the clonal relationship between these STICs and HGSCs by performing next-generation targeted sequencing.

Results Identical pathogenic mutations and loss of heterozygosity (LOH) of TP53 were identified in the STICs and HGSCs in five out of seven patients (71%) which confirms clonal relationship in these patients. The median interval for developing HGSC after RRSO was 59 months (range: 24–118 months). Four of the seven women died of HGSC. Of the three women still alive one has recurrent disease which was stable at the last visit. Two patients have no signs of recurrence 4 and 18 years after diagnosis respectively.

Conclusion Our results indicate that cells from STIC can shed into the peritoneal cavity and give rise to HGSC after long lag periods in BRCA1/2 GPV carriers, and argues in favor of the hypothesis that STIC lesions may metastasize.

Disclosures No.

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