title: Clonality analysis of combined Brenner and mucinous tumours of the ovary reveals their monoclonal origin.
abstract: The derivation of ovarian intestinal-type mucinous tumours is not well established. Some are derived from teratomas but the origin of the majority is not clear. It has been recently proposed that the non-germ cell group may be derived from Brenner tumours, as the association of a mucinous tumour with a Brenner tumour is frequently observed. In order to explore the histogenesis of these neoplasms, we undertook a clonality analysis of the two components of ten combined Brenner and mucinous tumours using a human androgen receptor gene (HUMARA) assay. All eight informative cases of ten showed a concordant X-chromosome inactivation pattern between the two tumour components, indicative of a shared clonal origin (p = 0.0039). Microsatellite genotyping in five of the combined tumours displayed an identical heterozygous pattern with paired Fallopian tube tissue, indicative of a somatic cell origin. In addition, paired box protein 8, a highly sensitive Müllerian epithelial marker, was not detected by immunohistochemistry in either tumour component in any of the ten tumours, suggesting that this subset of mucinous tumours does not originate from Müllerian-derived epithelium. In conclusion, this study demonstrates that in combined mucinous and Brenner tumours, there is a shared clonal relationship between the two different tumour components and suggests that some pure mucinous tumours may develop from a Brenner tumour in which the Brenner tumour component becomes compressed and obliterated by an expanding mucinous neoplasm.
authors.affiliation: Department of Pathology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.|Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Yihong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.|Department of Pathology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Ren-chin
authors.initials: RC
authors.lastname: Wu
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Lauren Ende
authors.initials: LE
authors.lastname: Shwartz
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Haley
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Ming-tse
authors.initials: MT
authors.lastname: Lin
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.|Department of Gynecology and Obstetrics, Johns Hopkins Medical Institutions, Baltimore, MD, USA.|Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Ie-ming
authors.initials: IeM
authors.lastname: Shih
authors.affiliation: Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.|Department of Gynecology and Obstetrics, Johns Hopkins Medical Institutions, Baltimore, MD, USA.|Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Kurman
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D001706:Biopsy; D001948:Brenner Tumor / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D041321:Chromosomes, Human, X; D060965:Clonal Evolution; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D007150:Immunohistochemistry; D018895:Microsatellite Repeats; D008875:Middle Aged; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors / Q000032:analysis; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011944:Receptors, Androgen / Q000235:genetics; D049951:X Chromosome Inactivation
chemical_list: C410798:AR protein, human; D014408:Biomarkers, Tumor; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors; D011944:Receptors, Androgen
keywords: Brenner tumour; HUMARA; X-chromosome inactivation; clonality analysis; histogenesis; mucinous tumour; ovary