Increased incidence of brain metastases in BRCA1-related ovarian cancers.
OBJECTIVE
Brain metastasis from ovarian cancer is a very rare phenomenon. BRCA1-related ovarian cancers show specific pathobiological profiles, advanced stage, and sensitivity to chemotherapeutic agents. However, no clear relationship to any known metastatic behavior has yet been found, so we examined the BRCA1 mutation and expression profiles in ovarian cancer cases with brain metastases.


METHODS
We examined our clinical records of 340 ovarian cancer cases from 1983 to 2007 to ascertain cases with brain metastases. In the molecular genetic analyses, we performed loss of heterozygosity (LOH), direct sequence and immunohistochemical staining analysis of BRCA1.


RESULTS
We ascertained seven cases with brain metastases in 340 ovarian cancer cases (7/340=2.1%). Among the seven cases, three cases had ovarian and/or breast cancer patients in third-degree relatives. We detected four LOH-positive cases and a germline mutation of BRCA1 in two of the four cases. Furthermore, the remaining two cases showed absent staining of the BRCA1 protein. Therefore, four of seven cases with brain metastases were considered BRCA1-related ovarian cancers (4/7=57.1%). All four of the cases were serous adenocarcinoma.


CONCLUSIONS
Our results suggest that the loss of BRCA1 function may be involved in the phenomenon of brain metastasis from ovarian cancer. Further molecular biologic analyses will be required for a better understanding of this rare phenomenon.
Department of Obstetrics and Gynecology, Niigata University Graduate School of Medical and Dental Science, Niigata, Japan.
Masayuki
M
Sekine
Kosuke
K
Yoshihara
Dai
D
Komata
Kazufumi
K
Haino
Koji
K
Nishino
Kenichi
K
Tanaka
D000328:Adult; D019313:BRCA1 Protein / Q000235:genetics* / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000453:epidemiology* / Q000235:genetics / Q000556:secondary; D018284:Cystadenocarcinoma, Serous / Q000453:epidemiology* / Q000235:genetics / Q000556:secondary; D005260:Female; D019398:Genes, BRCA1; D018095:Germ-Line Mutation; D006801:Humans; D015994:Incidence; D019656:Loss of Heterozygosity; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
D019313:BRCA1 Protein