TY - JOUR
T1 - Ovarian Brenner tumour
T2 - A morphologic and immunohistochemical analysis suggesting an origin from fallopian tube epithelium
AU - Kuhn, Elisabetta
AU - Ayhan, Ayse
AU - Shih, Ie Ming
AU - Seidman, Jeffrey D.
AU - Kurman, Robert J.
N1 - Funding Information:
The authors thank Ms. Asli Bahadirli-Talbott and Ms. Nichelle Gray for their excellent technical assistance. This study was supported by OSB1 grant from HERA foundation, and CDMRP Grant (No. OC100517) from the US Department of Defense.
Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 2013/12
Y1 - 2013/12
N2 - Background Brenner tumours (BTs), like other epithelial ovarian tumours, are thought to develop from the ovarian surface epithelium. Aim and Methods 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.
AB - Background Brenner tumours (BTs), like other epithelial ovarian tumours, are thought to develop from the ovarian surface epithelium. Aim and Methods 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.
KW - Brenner tumour
KW - Histogenesis
KW - Metaplasia
KW - Ovarian tumour
KW - Pathogenesis
KW - Transitional
KW - Tuboperitoneal junction
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U2 - 10.1016/j.ejca.2013.08.011
DO - 10.1016/j.ejca.2013.08.011
M3 - Article
C2 - 24012099
AN - SCOPUS:84887999934
SN - 0959-8049
VL - 49
SP - 3839
EP - 3849
JO - European Journal of Cancer
JF - European Journal of Cancer
IS - 18
ER -