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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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.
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