Molecular evidence linking primary cancer of the Fallopian tube to BRCA1 germline mutations

Objectives. BRCA1 and BRCA2 germline mutations increase the risk of ovarian and breast cancer. Fallopian tube cancer has occasionally been observed in breast-ovarian cancer families. At our family cancer clinic we recently en countered two cases of Fallopian tube cancer within two families harboring a BRCA1 germline mutation. To study the relationship between Fallopian tube cancer and BRCA1 mutations, a histopathological reevaluation and molecular analysis were performed. Methods. Medical and histopathological reports of the Fallopian tube cancer cases as well as archival tissue blocks were retrieved. The histopathologi cal diagnoses were reevaluated. We investigated whether patients with Fallo pian tube cancer had been carriers of a BRCA germline mutation. In addition we investigated whether loss of the wild-type allele had occurred in the t umor. Results. In 2 of 23 families with a known BRCA1 mutation from our family ca ncer clinic, a case of Fallopian tube cancer was reported. Histological ree valuation confirmed the diagnosis of Fallopian tube cancer in both cases. I n one case Fallopian tube cancer may have been part of a multifocal primary malignancy. In both patients the presence of a BRCA1 mutation was confirme d in the germline. Furthermore, we showed loss of the wild-type BRCA1 allel e in both tumors. Conclusions. These findings provide the first molecular evidence that Fallo pian tube cancer may be due to germline mutations in BRCA1. This may have i mportant consequences for the preferred method of prophylactic oophorectomy in BRCA1 mutation carriers. (C) 2000 Academic Press.