Immunohistochemical analyses of sporadic and familial (185delAG carriers) ovarian cancer in Israel.
A single germ line mutation in BRCA1, (185delAG) is detected in a substantial portion of Jewish Israeli patients with ovarian cancer. Whether disease phenotypes differ in BRCA1 mutation carriers and sporadic cases is presently a subject for debate. To gain insight into this issue, we analysed tumours from 65 Jewish women with ovarian cancer, 29 (45%) were 185delAG BRCA1 mutation carriers, and 36 (55%) were non-carriers of any of the predominant Jewish mutations in BRCA1 or BRCA2 (sporadic). In 19/29 mutation carriers (66%) diagnosis was made prior to age 60 years, compared with 14/36 (39%) of the non-carriers (P=0.03; Yates corrected P=0.06). Low malignant potential ('borderline') tumours were detected less frequently among carriers (2/29; 7%) than non-carriers (9/36; 25%) (P=0.03; one tail P=0.05). Immunohistochemical analysis in invasive carcinoma (n=54) showed that 17/27 carriers (63%) and 18/27 non-carriers (67%) had positive nuclear staining with a p53 antibody. In 4/27 carriers (15%) and 3/25 non-carriers (12%), 25% or more of the tumour cells stained positive for Ki-67, an insignificant difference. Results were not altered by including borderline tumours (n=11) in these analyses. We conclude that the rate of TP53 inactivation and proliferative index in ovarian cancer, are similar for 185delAG BRCA1 mutation carriers and sporadic cases.
Ravid
A
A
Department of Surgery, Elias Sourasky Medical Center, Ichilov, Tel-Aviv, Israel.
Barshack
I
I
Hirsh-Yechezkel
G
G
Goldberg
I
I
Bar-Sade
R B
RB
Chetrit
A
A
Reder
I
I
Ben-Baruch
G
G
Gotlieb
W H
WH
Kopolovic
J
J
Friedman
E
E
Barschack
I
I
Koplovic
J
J
D000368:Aged; D024682:BRCA2 Protein; D005260:Female; D019398:Genes, BRCA1; D018095:Germ-Line Mutation / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D007150:Immunohistochemistry; D007585:Jews / Q000235:genetics*; D019394:Ki-67 Antigen / Q000032:analysis; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics*; D010375:Pedigree; D011379:Prognosis; D014157:Transcription Factors / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D024682:BRCA2 Protein; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53