Tubal epithelial lesions in salpingo-oophorectomy specimens of BRCA-mutation carriers and controls

Mingels, Marjanka J.J.M.; Roelofsen, Thijs; Laak, Jeroen van der; Hullu, Joanne A. de; Ham, Maaike A.P.C. van; Massuger, Leon F.A.G.; Bulten, Johan; Bol, Mijke

doi:10.1016/j.ygyno.2012.06.015

Cited by 61 publications

(40 citation statements)

References 34 publications

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“…Our findings support the hypothesis that the fallopian tube, specifically the distal portion, is the dominant site of origin of pelvic serous carcinomas in BRCA mutation carriers. Diagnosis of STIC in 12% of the 78 BRCA mutation carriers in this study is consistent with reports of occult carcinomas in 5-10% of adnexa from BRCA mutation carriers who undergo RRSO [5][6][7][8]12,18,21,25]. STIC was more frequent in BRCA1 than in BRCA 2 mutation carriers in this cohort, 13% versus 8% respectively, although the significance of this finding is limited by the small number of BRCA2 mutation carriers.…”

Section: Discussionsupporting

confidence: 90%

“…Comprehensive pathologic assessment of the fallopian tubes of BRCA mutation carriers has enhanced the detection of occult carcinomas; however, it has also resulted in the discovery of several serous tubal epithelial lesions of uncertain significance, that might represent benign proliferations of the tubal epithelium [7,21]. Some lesions have been endorsed as potential candidate precursors to serous carcinoma in BRCA mutation carriers without information describing their occurrence and distribution in control patients, who are not BRCA mutation carriers.…”

Section: Contents Lists Available At Sciencedirectmentioning

confidence: 99%

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A cautious view of putative precursors of serous carcinomas in the fallopian tubes of BRCA mutation carriers

Cass

Walts

Barbuto

et al. 2014

Gynecologic Oncology

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Section: Discussionsupporting

confidence: 90%

Section: Contents Lists Available At Sciencedirectmentioning

confidence: 99%

A cautious view of putative precursors of serous carcinomas in the fallopian tubes of BRCA mutation carriers

Cass

Walts

Barbuto

et al. 2014

Gynecologic Oncology

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“…In the case of highgrade serous subtype tumors specifically, there is now considerable evidence that these lesions often arise in lining epithelium of the distal portion of the fallopian tubes, which is very closely related, developmentally, to the OSE (11). The fallopian tube origin of high-grade serous tumors has many implications for clinical management, including changes to surgical intervention protocols for women who are BRCA1 mutation carriers who choose prophylactic early lesion removal before frank tumor diagnosis (12). In addition, it indicates that the cells of frank high-grade serous tumors have likely already been shed into the fluid of the peritoneal cavity and then later attach to either to the ovarian surface or the abdominopelvic wall where they are most often first discovered (13).…”

Section: Introductionmentioning

confidence: 99%

Microenvironmental Regulation of BRCA1 Gene Expression by c-Jun and Fra2 in Premalignant Human Ovarian Surface Epithelial Cells

Zhou

Graves

MacDonald

et al. 2013

Molecular Cancer Research

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Reduced BRCA1 gene expression is common in the sporadic form of ovarian carcinoma. The spread of this highly lethal cancer often begins when tumor cell clusters are shed into the fluid of the abdominopelvic cavity such that they can float freely before seeding distant sites on the peritoneal walls and organs. Thus, the microenvironment that tumor cells find themselves in changes dramatically during these early shedding and floating stages of transperitoneal metastasis. To mimic this microenvironmental change in vitro, we released premalignant human ovarian surface epithelial cells from the substratum and forced them to cluster in suspension. Under these conditions, steady state levels of BRCA1 mRNA and protein fell significantly and the transcriptional activation state of the BRCA1 promoter was suppressed. Analysis of the promoter indicated that the previously identified "CRE" element located within the "positive regulatory region" (PRR) contributed to this suppression. More specifically, we show that the suppression was mediated, at least in part, by a suspension culture-driven decrease in the levels of two members of the AP1 transcription factor complex, c-Jun and Fra2, that bind to the CRE element. Therefore, a microenvironmental change that is manifested during the initial stages of ovarian carcinoma dissemination may, potentially, help suppress BRCA1 expression in sporadic tumors and thus promote their progression. Mol Cancer Res; 11(3); 272-81. Ó2013 AACR. IntroductionEpithelial ovarian carcinoma is the leading cause of death due to gynecologic malignancy (1). The great majority of these deaths occur in women who present with high-grade serous subtype tumors that metastasize by spreading transperitoneally through the abdominopelvic cavity. High-grade serous subtype tumors are also notable because they also have the highest rate of BRCA1 abnormalities, a considerable proportion of which occur due to epigenetic silencing rather than mutation (2). Given BRCA1 0 s myriad roles in acting to maintain genomic stability and differentiation, determining

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“…10,33 Tubal hyperplasia and minor epithelial atypia were equally present in women at risk of ovarian carcinoma compared with women from normal populations, and considered as variants of normal tubal epithelial proliferation. 22 Recently, the introduction of the SEE-Fim protocol resulted in a significant increase of the identification of serous tubal intraepithelial carcinoma, as it enabled optimal microscopic view of the tubal plicae. 19 The endometrium is not particularly difficult to visualize microscopically, but its heterogeneous aspect and the small size of some lesions necessitates meticulous screening.…”

Section: Discussionmentioning

confidence: 99%

“…22 Tubal hyperplasia was defined as cellular crowding in absence of atypical nuclei, and minor epithelial atypia as cellular crowding, with slight cellular atypia and nuclei with small nucleoli, but without loss of polarity. Serous tubal intraepithelial carcinoma is defined as noninvasive, serous carcinoma resembling cells that replace the tubal epithelium.…”

Section: Study Design and Case Selectionmentioning

confidence: 99%

Müllerian precursor lesions in serous ovarian cancer patients: using the SEE-Fim and SEE-End protocol

et al. 2014

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Serous ovarian cancer is suggested to develop from epithelium embryologically derived from the Mü llerian ducts. The aim of the current study is to thoroughly, analyze the epithelium derived from the Mü llerian ducts (cervix, endometrium and fallopian tubes) in serous ovarian cancer patients. Sixty women diagnosed with serous ovarian carcinoma were included in this multicentre, observational study. Tissues were embedded completely for histological assessment, in accordance with the SEE-Fim and SEE-End protocol (Sectioning and Extensively Examining of the Fimbriated end; and-Endometrium), and prevalence of cervical, as well as endometrial and tubal pathology was analyzed. In 31 (52%) cases, a pathologic lesion was identified, and in 16 (27%) of these cases coexistence of pathologic lesions. In 1 case, severe dysplasia was found in the cervix, in 9 (15%) cases endometrial intraepithelial carcinoma, in 19 (32%) cases atypical hyperplasia, and in 23 (43%) cases serous tubal intraepithelial carcinoma. Serous tubal intraepithelial carcinoma was seen significantly more often concurrent with endometrial atypical hyperplasia or endometrial intraepithelial carcinoma than with benign endometrium (64 vs 28%; P ¼ 0.01). To conclude, histological assessment of epithelium derived from Mü llerian ducts of serous ovarian cancer patients resulted in the identification of endometrial intraepithelial carcinoma, serous tubal intraepithelial carcinoma and/or endometrial atypical hyperplasia in more than half of cases. Coexistence of these pathologic lesions was common, and might represent an effect of field carcinogenesis or tumor implantation of migrating cells.

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Tubal epithelial lesions in salpingo-oophorectomy specimens of BRCA-mutation carriers and controls

Cited by 61 publications

References 34 publications

A cautious view of putative precursors of serous carcinomas in the fallopian tubes of BRCA mutation carriers

A cautious view of putative precursors of serous carcinomas in the fallopian tubes of BRCA mutation carriers

Microenvironmental Regulation of BRCA1 Gene Expression by c-Jun and Fra2 in Premalignant Human Ovarian Surface Epithelial Cells

Müllerian precursor lesions in serous ovarian cancer patients: using the SEE-Fim and SEE-End protocol

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