Does serous tubal intraepithelial carcinoma (STIC) metastasize? The clonal relationship between STIC and subsequent high-grade serous carcinoma in BRCA1/2 mutation carriers several years after risk-reducing salpingo-oophorectomy.

Autor: van den Berg CB; Department of Gynecologic Oncology, Erasmus MC Cancer Center, University Medical Center, Rotterdam, the Netherlands. Electronic address: c.vandenberg@erasmusmc.nl., Dasgupta S; Department of Pathology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands; Imaging Platform, Broad Institute of MIT and Harvard, Cambridge, United States., Ewing-Graham PC; Department of Pathology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands., Bart J; Department of Pathology, University Medical Center Groningen, University of Groningen, the Netherlands., Bulten J; Department of Pathology, Radboud University Medical Center, Nijmegen, the Netherlands., Gaarenstroom KN; Department of Gynecologic Oncology, Leiden University Medical Center, Leiden, the Netherlands., de Hullu JA; Department of Gynecologic Oncology, Radboud University Medical Center, Nijmegen, the Netherlands., Mom CH; Department of Gynecologic Oncology, Cancer Center Amsterdam, Amsterdam University Medical Center, Center for Gynecologic Oncology Amsterdam, the Netherlands., Mourits MJE; Department of Gynecologic Oncology, University Medical Center Groningen, University of Groningen, the Netherlands., Steenbeek MP; Department of Gynecologic Oncology, Radboud University Medical Center, Nijmegen, the Netherlands., van Marion R; Department of Pathology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands., van Beekhuizen HJ; Department of Gynecologic Oncology, Erasmus MC Cancer Center, University Medical Center, Rotterdam, the Netherlands.
Jazyk: angličtina
Zdroj: Gynecologic oncology [Gynecol Oncol] 2024 Aug; Vol. 187, pp. 113-119. Date of Electronic Publication: 2024 May 17.
DOI: 10.1016/j.ygyno.2024.05.010
Abstrakt: Objective: The majority of high-grade serous carcinomas (HGSC) of the ovary, fallopian tube, and peritoneum arise from the precursor lesion called serous tubal intraepithelial carcinoma (STIC). It has been postulated that cells from STICs exfoliate into the peritoneal cavity and give rise to peritoneal HGSC several years later. While co-existent STICs and HGSCs have been reported to share similarities in their mutational profiles, clonal relationship between temporally distant STICs and HGSCs have been infrequently studied and the natural history of STICs remains poorly understood.
Methods: We performed focused searches in two national databases from the Netherlands and identified a series of BRCA1/2 germline pathogenic variant (GPV) carriers (n = 7) who had STIC, and no detectable invasive carcinoma, at the time of their risk-reducing salpingo-oophorectomy (RRSO), and later developed peritoneal HGSC. The clonal relationship between these STICs and HGSCs was investigated by comparing their genetic mutational profile by performing next-generation targeted sequencing.
Results: Identical pathogenic mutations and loss of heterozygosity of TP53 were identified in the STICs and HGSCs of five of the seven patients (71%), confirming the clonal relationship of the lesions. Median interval for developing HGSC after RRSO was 59 months (range: 24-118 months).
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.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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