LETTER TO THE EDITOR
BRCA1 Immunohistochemistry Assay: Can it Play
a Role in Assessing Sporadic Early-Onset Breast Cancer?
To the Editor:
Much has been published about the relationship
between BRCA1 mutation and familial breast cancer
(BC). Some researchers have found an association
between altered BRCA1 immunohistochemical (IHC)
expression in sporadic early-onset BC (1,2) and
clinicopathological features indicative of poor progno-
sis (3,4). Studies have also shown that BRCA1 IHC and
immunocytochemical approaches could be used as
screening strategies to identify gene mutation carriers
(5,6). On reviewing the expression of biomarkers in BC
and their use in a molecular classification of the condi-
tion, Rakha et al. (7) found immunohistochemistry par-
ticularly effective, allowing in situ analysis with direct
morphological control of the biomarker distribution.
We are currently studying IHC biomarkers in young
patients with sporadic BC. We have analyzed BRCA1
IHC expression and compared it with the expression of
other IHC markers (ER, PR, HER2, vimentin, and
34bE12), tumor grade, and stage. Our patients are
from southern Brazil, a region characterized by an
extremely high annual incidence of BC (127 cases per
100,000 women) and where a rising incidence of the
disease in patients younger than 40 years of age has
been observed over the last two decades (8,9).
To date, we have analyzed the expression of a
BRCA1 polyclonal antibody (Biogenex, San Ramon,
CA) in paraffin-embedded primary BC samples from
119 patients in the following age groups: up to 35 years
old (n = 32); 36–40 years (n = 47); older than 55 years
(n = 40). Patients up to 40 years of age more frequently
presented advanced tumor stages (III and IV)
(p = 0.04). In the youngest group, the rate of loss of
nuclear BRCA1 IHC expression was 20% higher than
in the oldest one (p = 0.75). A new evaluation of the
sample distribution in five age groups indicated a
Address correspondence and reprint requests to: Adriana Vial Roehe,
PhD, Rua Sarmento Leite, 245, Sala 10, 90050170 Porto Alegre, Brazil, or
e-mail: aroehe@gmail.com.
DOI: 10.1111/j.1524-4741.2012.01292.x
ª 2012 Wiley Periodicals, Inc., 1075-122X/12
The Breast Journal, Volume 18 Number 5, 2012 500–501
proportional decrease in antibody nuclear expression
with increasing age (p = 0.05). Correlating cytokeratin
34bE12 (DakoCytomation, Carpinteria, CA) with
BRCA1 results, we observed that 15 (62.5%) of 24
BRCA1 IHC-negative cases were positive to 34bE12.
Our preliminary data suggest that the loss of BRCA1
nuclear staining could be involved in the pathogenesis
of sporadic early-onset BC and that it could be related
to the expression of basal cell markers.
Molecular methods are still the first choice in iden-
tifying BRCA1 mutations. Nevertheless, immunohisto-
chemistry could play a role in preliminary tests for
detecting reduction in BRCA1 nuclear expression,
especially in young patients and in regions of high BC
incidence. However, further studies are necessary to
elucidate the correlation of BRCA1 with different
IHC biomarkers in breast carcinogenesis.
Acknowledgments
This research received funding from the Brazilian
National Governmental Agency for Research Improve-
ment (CAPES). The authors have no conflict of inter-
est and are fully responsible for all decisions regarding
the content of this study.
Adriana Vial Roehe, PhD*
Ana Letı́cia Boff, MD 
and Andréa Damin, PhDà
*Department of Pathology, Universidade Federal de
Ciências da Saúde de Porto Alegre (UFCSPA),
Porto Alegre, Brazil;
 
Division of Pathology Graduate Program, Universid-
ade Federal de Ciências da Saúde de Porto Alegre
(UFCSPA), Porto Alegre, Brazil;
à
and Hospital Fêmina, Grupo Hospitalar Conceição
(GHC), Porto Alegre, Brazil
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