title: Ovarian Brenner tumour: a morphologic and immunohistochemical analysis suggesting an origin from fallopian tube epithelium.
abstract: BACKGROUND
  Brenner tumours (BTs), like other epithelial ovarian tumours, are thought to develop from the ovarian surface epithelium.
  
  
  OBJECTIVE
  We hypothesised that BTs arise from transitional metaplasia near the tuboperitoneal junction which, when embedded in the ovary as Walthard cell nests, may progress to BTs. The aim of this study was to validate this hypothesis by a morphologic and immunohistochemical (IHC) analysis.
  
  
  RESULTS
  The IHC analysis revealed that fallopian tube secretory cells, transitional metaplasia, Walthard cell nests and the epithelial component of BTs shared a similar IHC profile, consistently expressing AKR1C3 (an enzyme involved in androgen biosynthesis) and androgen receptor, but not calretinin. The tumour stromal cells that immediately surrounded the epithelial nests showed strong expression of calretinin, inhibin and steroidogenic factor 1 (markers of steroidogenic cells) in the majority of BTs. Using a highly sensitive immunofluorescent staining method, we detected small groups of cilia in transitional metaplasia and Walthard cell nests, multifocal stretches of cilia and/or ciliated vacuoles in benign BTs and well-developed cilia in atypical proliferative BTs.
  
  
  CONCLUSIONS
  Our findings suggest a tubal origin of BTs through transitional metaplasia and Walthard cell nests, based on their anatomic proximity, similar IHC profile and the presence of cilia. In addition, we hypothesise a role of androgenic stimulation in the pathogenesis of BT, based on the IHC staining pattern of calretinin, inhibin and steroidogenic factor 1 expressed in the luteinised stromal cells surrounding the epithelial nests of the tumours, and AKR1C3 and androgen receptor expressed in both the epithelial and stromal components.
authors.affiliation: Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA. Electronic address: elisabettakuhn@hotmail.it.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Kuhn
authors.forename: Ayse
authors.initials: A
authors.lastname: Ayhan
authors.forename: Ie-Ming
authors.initials: IeM
authors.lastname: Shih
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Seidman
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Kurman
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000074425:Aldo-Keto Reductase Family 1 Member C3; D001948:Brenner Tumor / Q000378:metabolism* / Q000473:pathology; D064032:Calbindin 2 / Q000378:metabolism; D002923:Cilia / Q000737:chemistry / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D004848:Epithelium / Q000737:chemistry* / Q000473:pathology; D005187:Fallopian Tubes / Q000737:chemistry* / Q000473:pathology; D005260:Female; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000378:metabolism; D007150:Immunohistochemistry; D007265:Inhibins / Q000378:metabolism; D008679:Metaplasia / Q000378:metabolism / Q000473:pathology; D008856:Microscopy, Fluorescence; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D010053:Ovary / Q000737:chemistry / Q000473:pathology; D011944:Receptors, Androgen / Q000378:metabolism; D054339:Steroidogenic Factor 1 / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology
chemical_list: C576764:CALB2 protein, human; D064032:Calbindin 2; D011944:Receptors, Androgen; D054339:Steroidogenic Factor 1; D007265:Inhibins; D015096:3-Hydroxysteroid Dehydrogenases; D006911:Hydroxyprostaglandin Dehydrogenases; C487341:AKR1C3 protein, human; D000074425:Aldo-Keto Reductase Family 1 Member C3
keywords: Brenner tumour; Histogenesis; Metaplasia; Ovarian tumour; Pathogenesis; Transitional; Tuboperitoneal junction