A Case of Uterine Serous Carcinoma in a Patient with a Germline BRCA1 Mutation: Genomic Profiling Reveals an Ovarian Cancer-Like Molecular Signature.

Uterine serous carcinoma (USC) is a highly aggressive histological subtype of endometrial cancer that causes almost 40% of deaths related to this cancer, despite accounting for only about 10% of cases of endometrial cancer. This high mortality rate is due to the high metastatic potential of USC and its resistance to treatment. Genetic alterations frequently associated with USC include mutations in TP53 and PIK3CA. BRCA1, a major causative gene of hereditary breast and ovarian cancer, may also contribute to the risk of USC. We describe a case of USC with a germline pathogenic BRCA1 mutation, and we review the literature in this area. The patient was a 50-year-old woman who had abnormal genital bleeding and was diagnosed with USC by endometrial biopsy. The patient had a history of metachronous breast cancer. Surgical treatment was performed, and a subsequent pathological examination of the resected specimen indicated serous carcinoma in the endometrium and high-grade serous carcinoma in the left fallopian tube. Immunohistochemical analysis confirmed that these tumors originated from different primary sites, leading to diagnosis of synchronous malignancies. Genetic testing identified a germline BRCA1 mutation, and comprehensive genomic profiling of the uterine tumor revealed additional pathogenic mutations in TP53, MAP3K1, RB1, and MYC. Some of these mutations are not common in USC, suggesting a unique genetic profile for USC associated with BRCA1 mutation. This finding suggests that BRCA1-associated USC may be sensitive to poly ADP-ribose polymerase inhibitors, and also raises the question of whether risk-reducing hysterectomy should be considered for patients with BRCA1 mutation. USC with a BRCA1 mutation may have molecular characteristics distinct from those of sporadic USC, and further accumulation and analysis of such cases are needed to evaluate the clinical implications.