Pathology of ovarian cancers in BRCA1 and BRCA2 carriers.
OBJECTIVE
Germline mutations in the BRCA1 and BRCA2 genes confer increased susceptibility to ovarian cancer. There is evidence that tumors in carriers may exhibit a distinct distribution of pathological features, but previous studies on the pathology of such tumors have been small. Our aim was to evaluate the morphologies and immunophenotypes in a large cohort of patients with familial ovarian cancer.


METHODS
We performed a systematic review of ovarian tumors from 178 BRCA1 mutation carriers, 29 BRCA2 mutation carriers, and 235 controls with a similar age distribution. Tumors were evaluated by four pathologists blinded to mutation status. Both morphological features and immunochemical staining for p53 and HER2 were evaluated.


RESULTS
Tumors in BRCA1 mutation carriers were more likely than tumors in age-matched controls to be invasive serous adenocarcinomas (odds ratio, 1.84; 95% confidence interval, 1.21-2.79) and unlikely to be borderline or mucinous tumors. Tumors in BRCA1 carriers were of higher grade (P < 0.0001), had a higher percentage solid component (P = 0.001), and were more likely to stain strongly for p53 (P = 0.018). The distribution of pathological features in BRCA2 carriers was similar to that in BRCA1 carriers.


CONCLUSIONS
Use of pathological features can substantially improve the targeting of predictive genetic testing. Results also suggest that BRCA1 and BRCA2 tumors are relatively aggressive and may be expected to have poor prognosis, although this may be treatment dependent.
Lakhani
Sunil R
SR
The Breakthrough Toby Robins Breast Cancer Research Centre, Institute of Cancer Research, London, United Kingdom. Sunil.Lakhani@icr.ac.uk
Manek
Sanjiv
S
Penault-Llorca
Frederique
F
Flanagan
Adrienne
A
Arnout
Laurent
L
Merrett
Samantha
S
McGuffog
Lesley
L
Steele
Dawn
D
Devilee
Peter
P
Klijn
Jan G M
JG
Meijers-Heijboer
Hanne
H
Radice
Paolo
P
Pilotti
Silvana
S
Nevanlinna
Heli
H
Butzow
Ralf
R
Sobol
Hagay
H
Jacquemier
Jocylyne
J
Lyonet
Dominique Stoppa
DS
Neuhausen
Susan L
SL
Weber
Barbara
B
Wagner
Teresa
T
Winqvist
Robert
R
Bignon
Yves-Jean
YJ
Monti
Franco
F
Schmitt
Fernando
F
Lenoir
Gilbert
G
Seitz
Susanne
S
Hamman
Ute
U
Pharoah
Paul
P
Lane
Geoff
G
Ponder
Bruce
B
Bishop
D Timothy
DT
Easton
Douglas F
DF
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D024682:BRCA2 Protein / Q000235:genetics*; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D019398:Genes, BRCA1; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D016015:Logistic Models; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D024682:BRCA2 Protein; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53