FISH analysis of BRCA1 copy number in paraffin-embedded ovarian cancer tissue samples.
We investigated the BRCA1 gene copy number in unselected ovarian malignancies. Both additional genes (amplification) as well as deletion (loss of heterozygosity, LOH) are often thought to have a role in the initiation or progression of cancer. In addition, if there were little change, deletion studies might help identify BRCA1 mutation carriers. Forty-seven paraffin-embedded ovarian tissue blocks obtained between 1984 and 1997 were used for this study. A sample was "deletion-positive" when BRCA1-deleted cells in the tumor area were significantly different from the benign area. Twenty-five (53%) cases were found to be "deletion-positive". The average age of onset of "deletion-positive" patients was 50.8 years and of "deletion-negative" 57.8 years (P < 0.05). There was no statistical difference between groups in the staging, histology, or prognosis. A Kaplan-Meier study did show a trend towards poorer survival for "deletion-positive" patients. FISH permits unique molecular characterization of malignancies at a cellular level. Double amplification of HER-2 and c-myc predicts poor ovarian cancer survival. There appears to be a definite role for BRCA1 deletion in reducing the age of ovarian cancer onset and possibly in overall survival. Further FISH studies of this and other patient sets using additional molecular markers are needed.
Kato
Hisanori
H
Department of Gynecology and Obstetrics, Nagoya City Hospital, 4670027 Japan. q-kato@wc4.so-net.ne.jp
Arakawa
Atsushi
A
Suzumori
Kaoru
K
Kataoka
Nobuhiko
N
Young
S Robert
SR
D000328:Adult; D017668:Age of Onset; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D018628:Gene Dosage; D019398:Genes, BRCA1; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000401:mortality; D016612:Paraffin Embedding; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012189:Retrospective Studies
D004273:DNA, Neoplasm