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Abstract
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.
