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Tubal histopathological abnormalities in BRCA1/2 mutation carriers undergoing prophylactic salpingo-oophorectomy: a case–control study
  1. Federica Sina1,
  2. Chiara Cassani2,
  3. Chiara Comerio3,
  4. Elena De Ponti4,
  5. Francesca Zanellini2,
  6. Martina Delle Marchette3,
  7. Gaia Roversi3,5,
  8. Marta Jaconi6,
  9. Eloisa Arbustini7,
  10. Mario Urtis7,8,
  11. Cristina Dell’Oro3,
  12. Benedetta Zambetti3,
  13. Cristiana Paniga3,
  14. Eleonora Acampora3,
  15. Serena Negri3,
  16. Sara Lazzarin3,
  17. Stefania Cesari9,
  18. Arsenio Spinillo2,
  19. Joanne Kotsopoulos10,11 and
  20. Robert Fruscio1,3
  1. 1Department of Surgery, Gynecological Surgery Unit, San Gerardo Hospital, Monza, Lombardia, Italy
  2. 2Gynecology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Lombardia, Italy
  3. 3Department of Medicine and Surgery, University of Milan-Bicocca, Milan, Lombardia, Italy
  4. 4Department of Physical Medicine, San Gerardo Hospital, Monza, Italy
  5. 5Department of Pathology, Unit of Genetics, San Gerardo Hospital, Monza, Italy
  6. 6Department of Pathology, San Gerardo Hospital, Monza, Lombardia, Italy
  7. 7Center for Inherited Cardiovascular Disease, Fondazione IRCCS Policlinico San Matteo, Pavia, Lombardia, Italy
  8. 8Department of Industrial and Information Engineering, University of Pavia, Pavia, Italy
  9. 9Pathology Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Lombardia, Italy
  10. 10Women’s College Research Institute, Women's College Hospital, Toronto, Ontario, Canada
  11. 11Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
  1. Correspondence to Professor Robert Fruscio, Department of Surgery, Gynecological Surgery Unit, San Gerardo Hospital, 20900 Monza, Italy; robert.fruscio{at}


Objective To describe tubal histopathological abnormalities in women with germline BRCA1/2 mutations and in controls.

Methods Consecutive women with BRCA1/2 mutations undergoing bilateral salpingo-oophorectomy between 2010 and 2020 in two centers (San Gerardo Hospital, Monza and San Matteo Hospital, Pavia) were considered in this analysis and compared with controls who had the same surgical procedure for benign conditions. Frequency of p53 signature, serous tubal intraepithelial carcinoma, and high-grade serous ovarian cancer were compared between the two groups.

Results A total of 194 women with pathogenic BRCA1/2 mutations underwent prophylactic salpingo-oophorectomy. Of these, 138 women (71%) had a completely negative histological examination, while in 56 (29%) patients an ovarian or tubal alteration was reported. Among controls, 84% of patients had a p53wt signature, while 16% had a p53 signature. There was no difference in the frequency of a p53 signature between cases and controls; however, women with BRCA1/2 mutations were more likely to have pre-malignant or invasive alterations of tubal or ovarian epithelium (p=0.015). Among mutation carriers, older age both at genetic testing and at surgery was associated with an increased risk of having malignancies (OR=1.07, p=0.006 and OR=1.08, p=0.004, respectively). The risk of malignancy seems to be increased in patients with a familial history of high-grade serous ovarian cancer. Previous therapy with tamoxifen was significantly more frequent in patients with malignant lesions (40.0% vs 21.3%, p=0.006).

Conclusion We found that a p53 signature is a frequent finding both in BRCA1/2 mutation carriers and in controls, while pre-invasive and invasive lesions are more frequent in BRCA1/2 mutation carriers. Genetic and clinical characteristics are likely to affect the progression to malignancy.

  • BRCA1 protein
  • BRCA2 protein
  • ovarian diseases
  • gynecologic surgical procedures

Data availability statement

Data are available upon reasonable request.

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Data availability statement

Data are available upon reasonable request.

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  • FS and CCa contributed equally.

  • Contributors FS, CCa, JK, RF: Conceptualization. CCo, FZ, MDM, CD, BZ, CP, EAc, SN, SL: Data curation. EDP, RF: Formal analysis. FS, CCa, GR, MJ, EAr, MU: Investigation. FS, CCa, AS, JK, RF: Writing - original draft. FS, CCa, CCo, EDP, FZ, MDM, GR, MJ, EAr, MU, CD, BZ, CP, EAc, SN, SL, SC, AS, JK, RF: Writing - review and editing. RF act as guarantor.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.