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Mod Pathol. 2019 Nov 6. doi: 10.1038/s41379-019-0401-y. [Epub ahead of print]

Two types of primary mucinous ovarian tumors can be distinguished based on their origin.

Author information

1
Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands. Michiel.Simons@radboudumc.nl.
2
Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
3
Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands.
4
Department of Pathology, University Medical Center Groningen, Groningen, The Netherlands.
5
Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands.
6
Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
7
Department of Pathology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
8
Department of Obstetrics and Gynecology, Radboud University Medical Center, Nijmegen, The Netherlands.
9
Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
10
Department of Gynecology and Obstetrics, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
11
Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.

Abstract

The origin of primary mucinous ovarian tumors is unknown. We explore the hypothesis that they originate from either Brenner tumors or teratomas and examine differences between the tumors that arise in these settings. A total of 104 Brenner tumor-associated mucinous tumors and 58 teratoma-associated mucinous tumors were analyzed. Immunohistochemistry for 21 antigens and fluorescence in situ hybridization for ERBB2 and MYC were performed. Genome-wide copy number analysis and mutation analysis for 56 cancer-related genes was carried out on a subset of mucinous ovarian tumors and their complementary Brenner tumor or teratoma. Patients with teratoma-associated mucinous tumors were significantly younger than patients with Brenner tumor-associated mucinous tumors (43 vs. 61 years). During progression from cystadenoma to atypical proliferative mucinous (borderline) tumor to carcinoma expression of typical gastrointestinal markers was increased in both Brenner tumor-associated and teratoma-associated mucinous tumors. Brenner tumor-associated mucinous tumors showed more frequently calcifications and Walthard cell nests, rarely expressed SATB2 and showed more often co-deletion of CDKN2A and MTAP. Teratoma-associated mucinous tumors were characterized by mucinous stromal dissection, SATB2 expression and RNF43 mutations. Other frequent mutations in both Brenner tumor-associated and teratoma-associated mucinous tumors were TP53 and KRAS mutations. Based on identical mutations or copy number profiles clonal relationships were indicated in two mucinous tumors and their associated Brenner tumor. Teratomas and Brenner tumors give rise to different subtypes of mucinous ovarian tumors. Subsequent progression pathways are comparable since both Brenner tumor-associated and teratoma-associated mucinous tumors develop a gastrointestinal immunophenotype during progression and show early mutations in KRAS and TP53. Teratoma-associated mucinous tumors may more closely resemble true gastrointestinal tumors, indicated by their expression of SATB2 and the presence of RNF43 mutations.

PMID:
31695154
DOI:
10.1038/s41379-019-0401-y

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