Carcinosarcomas (CSs) are biphasic neoplasms composed of high grade, malignant, epithelial and mesenchymal elements. The incidence of gynecological CSs (GCSs) is 0.4/100,000 women per year. Patients affected with GCSs have been occasionally reported in Hereditary Breast Ovarian Cancer (HBOC) families, including a few cases with pathogenic variants in BRCA1/BRCA2 genes. The prevalence and the association of GCSs in HBOC families have not been systematically investigated. Thus, we searched for families with GCSs in the HBOC registry of the National Cancer Institute of Milan. Eleven families, including four BRCA1-positive and four BRCA2-positive, presented a case of GCS. In the three BRCA1-mutated patients for whom surgical specimens were available, DNA fragment and sequencing analyses revealed the loss of the constitutionally wild-type BRCA1 allele. All tumors presented also TP53 mutations and stained positive for the expression of the protein product by immunohistochemistry. Our results suggest that GCSs may be found not infrequently in HBOC families and assimilate the analyzed CSs to BRCA1-related breast/ovarian carcinomas, where the above findings are frequently observed. Exploring the role of BRCA genes in prospective unselected series of GCSs might improve the knowledge of the genesis of these malignancies and guide the proposition of prophylactic surgery and targeted therapy.
Keywords: BRCA1-related cancers; Gynecological carcinosarcomas; TP53 alterations; germline mutations; loss of heterozygosity.
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