Expression of BRCA1 protein in breast cancer and its
Emad A. Rakha MD, PhD⁎, Somaia E. El-Sheikh MSc, Mona A. Kandil MD,
Maysa E. El-Sayed MD, Andrew R. Green PhD, Ian O. Ellis FRCPath
The Breast Unit, Department of Histopathology, Nottingham City Hospital, University of Nottingham, NG5 1PB Nottingham, UK
Received 17 August 2007; revised 24 September 2007; accepted 10 October 2007
Summary BRCA1 is a tumor suppressor gene which, when mutated, is associated with the development
of hereditary breast cancers. In sporadic tumors, although inherent gene mutations are rare, loss of
BRCA1, resulting from reduced expression or incorrect subcellular localization, is postulated to be
important. The purpose of the current study was to examine the expression and localization of BRCA1
protein and to assess its prognostic value, in a well-characterized series of unselected breast carcinomas.
We have examined BRCA1 in a series of invasive breast carcinoma (1940 cases) using tissue microarray
and immunohistochemistry, to evaluate its expression pattern and to correlate this with clinicopathologic
variables and patient outcome. In breast cancer, complete loss of nuclear expression was observed in
223 cases (15%) and cytoplasmic expression was found in 541 breast cancers (36.6%). Absent or
reduced nuclear BRCA1 expression was observed more frequently in ductal carcinoma of no special
type and medullary-like carcinoma and less frequently in lobular and tubular mixed carcinomas. It was
also associated with high-grade, advanced lymph node stage, larger size, vascular invasion, negative
estrogen receptor, progesterone receptor and androgen receptor expression, and positive p53 and P-
cadherin expression, and with the basal-like class of breast cancer. Altered BRCA1 was associated with
shorter disease-free interval. Cytoplasmic expression was also associated with development of
recurrence and positive EGFR and HER2 expression. It showed an inverse association with survival
particularly in low-grade, small-size, and estrogen receptor–positive subgroups. In the grade 1
subgroup, multivariate analysis with adjustment for other prognostic factors showed that cytoplasmic
expression of BRCA1 was an independent predictor of disease-free interval. BRCA1 alteration may play
a significant role in the development and progression of breast cancer. Immunohistochemical assessment
of BRCA1 expression could provide additional clinically relevant information in routine classification
of breast cancer.
© 2008 Elsevier Inc. All rights reserved.
Breast cancer is the most common cancer and second
leading cause of cancer death among women in Western
countries . It is recognized to be biologically and
clinically heterogeneous. Thus, understanding its biology,
the ability to detect its growth potential, and assessment
⁎Corresponding author. Department of Histopathology, Nottingham
City Hospital, Hucknall Road, NG5 1PB Nottingham, UK.
E-mail address: firstname.lastname@example.org (E. A. Rakha).
0046-8177/$ – see front matter © 2008 Elsevier Inc. All rights reserved.
Human Pathology (2008) 39, 857–865
of certain prognostic factors are of great importance in
predicting disease outcome and planning treatment stra-
tegies. Moreover, additional molecular markers are being
sought to further refine classification of breast cancer,
especially in patient subgroups whose outcome cannot be
predicted accurately using conventional parameters. One
of the biomarkers that has received a great deal of
attention in breast cancer is the breast cancer suscept-
ibility gene-1 (BRCA1).
BRCA1 has been mapped to chromosome 17q21 . It
encodes a nuclear protein of 1863 amino acids  that
regulates, at least in part, transcriptional activation, DNA
repair, apoptosis, cell-cycle checkpoint control, and chro-
mosomal remodeling . In familial breast cancer, BRCA1 is
a classical tumor suppressor gene . The presence of
inherited mutations in BRCA1 continues to be one of the
best-defined overall risk factors for the development of
breast cancer; however, these familial mutations, together
with familial BRCA2 mutations, occur in less than 10% of all
diagnosed cases [5,6]. By definition, germline BRCA1 gene
mutations are virtually undetectable in sporadic breast
cancers , where some authors postulate that loss of
BRCA1 protein function, resulting from reduced expression
or incorrect subcellular localization, is important in these
tumors and provides evidence for the tumor suppressor
function [7-11] They suggest that it is involved in
carcinogenesis of these sporadic tumors via mechanisms
other than gene mutation. For example, there is some
evidence that epigenetic loss of BRCA1 function may
occur at the level of transcription or a subsequent step
affecting RNA accumulation  and promoter hyper-
Although the role of BRCA1 in hereditary breast cancers
and the characteristics of tumors with germline mutation
have been extensively studied, its role in sporadic tumors is
still not well defined and there remains controversy
regarding the significance of BRCA1 expression and its
subcellular localization among different studies. Some
studies have demonstrated a relationship between BRCA1-
associated breast cancer and development of distant
metastasis [14,15], and shorter disease-free survival ,
whereas others did not find any association with survival
 or other variables [12,16]. The subcellular localization
of BRCA1 has been reported to range from nuclear, to
cytoplasmic invaginations into the nucleus of the normal
cells, and to the abnormal cytoplasmic location [7-9,17,18].
These contradictory reports about the pattern of expression
may reflect differences in the specificity of antibodies used,
tissue fixation and immunostaining methods, and the
presence of different splice variant isoforms of BRCA1.
In this study, we have assessed, using immunohistochem-
istry (IHC), the expression of BRCA1 protein in a large and
well-characterized series of unselected breast cancer with a
long-term follow-up, prepared as tissue microarrays (TMA),
to evaluate the pattern of expression and the prognostic
significance of BRCA1 in this common cancer.
2. Materials and methods
2.1. Patients and tumors
A consecutive series of 1940 cases of invasive breast
carcinoma entered into the Nottingham Tenovus Primary
Breast Carcinoma Series between 1986 and 1998 were used.
This is a well-characterized series of primary operable
invasive breast cancer that has been previously used to study
a wide range of proteins [19-21]. Patients' clinical history
and cancer characteristics including tumor type ,
histologic grade , tumor size, lymph node (LN) status,
vascular invasion (VI), Nottingham Prognostic Index (NPI)
[24,25], and survival data including survival time (overall
survival [OS]), disease-free interval (DFI), recurrence, and
development of distant metastasis were available for all
patients. These patients were not selected on the basis of a
family history (eg, a known family history of breast and/or
ovarian cancer) or age at diagnosis.
In addition, data on postoperative chemotherapy and
hormonal therapy as well as other biomarkers including
estrogen receptor (ER), progesterone (PR) and androgen
(AR) receptors, p53, ERBB2 (HER2), EGFR (HER1),
ERBB3 (HER3), ERBB4 (HER4), P-cadherin, Bcl2, basal
cytokeratins (CKs) (CK5/6 and CK14), luminal CKs (CK7/8
and CK19), FHIT protein, MUC-1, and p21 expression
[21,26,27] were also available.
2.2. Tissue microarrays and IHC
TMAs were prepared as previously described . In
brief, tissue 0.6-mm-diameter cores were punched from
representative tumor regions of each donor block and arrayed
into a new recipient paraffin blocks using a tissue
microarrayer (Beecher Instruments, Sun Prairie, WI). TMA
blocks were constructed in duplicate, each containing one
sample from a different region of the tumor. TMA sections,
4 μm, were stained immunohistochemically using the
standard streptavidin-biotin complex method as previously
described [19,29,30]. Briefly, tissue slides were deparaffi-
nized with xylene and then rehydrated through 3 changes of
alcohol. Endogenous peroxidase activity was blocked by
incubation in a 0.3% hydrogen peroxide/methanol buffer.
Antigen retrieval was carried out by microwave treatment of
the slides in sodium citrate buffer (pH 6.0) for 20 minutes.
The slides were rinsed in Tris-buffered saline (TBS) (pH 7.6)
nonspecific staining. The slides were incubated for 1 hour
with the BRCA1 Ab-1, a mouse monoclonal antibody
directed against the amino terminal 304 amino acid residues
(clone, MS110, Oncogene Research Products, Cambridge,
MA, diluted at 1:150) . Several studies have confirmed
thereliability ofthis antibodyinformalin-fixed tumors andin
microwave antigen retrieval . Several blocking agents
were tested including normal swine serum, Marvel, and
858E. A. Rakha et al.
bovine serum albumin 1%. After washing with TBS, sections
were incubated with the secondary antibody (biotinylated
goat antimouse/rabbit immunoglobulin; Duet K 0492,
followed by the avidin-biotin complex (1:100) for a further
45 minutes. 3-3′Diaminobenzidine tetrahydrochloride (Dako
liquid DAB plus, K3468, Dako, Glostrup, Denmark) was
used as a chromogen with the addition of copper sulfate to
enhance staining. All sections were counterstained with
Mayer's hematoxylin. Positive (normal breast sections) and
negative control slides (according to manufacturer's data
sheet) were included in every experiment.
2.3. Evaluation of immunohistochemical staining
Of the 1940 breast cancer cases, sufficient tissue was
available to perform scoring in 1482 cases and these form the
basis of this study analysis. As controls, a whole tissue section
containing normal breast tissue was included, as well as any
normal glandular tissue entrapped in the cores. Assessment of
staining was based on a semiquantitative approach. A
modified histochemical score (H-score)  was used which
percentage of stained cells. For the intensity, a score index of
0, 1, 2, and 3 corresponding to negative, weak, moderate, and
strong staining intensity was used and the percentage of
positive cells at each intensity was estimated subjectively. A
final score of 0 to 300 is the product of both the intensity and
the percentage. In addition, assessment of the subcellular
localization and stromal expression was conducted. The
pattern of expression was nuclear, cytoplasmic, or combined
nuclear and cytoplasmic staining. Two cores were evaluated
from each tumor. Each core was scored individually, then the
mean of the 2 readings was calculated. If one core was
uninformative, either lost or contained no tumor tissues, the
overall score applied was that of the remaining core . The
cases were scored without knowledge of the patient outcome
by one observer on 2 separate occasions and a good
correlation between the results was found. For the purpose
of this study, positive expression of BRCA1 was identified by
nuclear expression was further stratified into 2 groups below
and above the median of expression (H-score = 100)
corresponding to reduced and strong expression. Cutoff
values for the other biomarkers included in this study were
chosen before statistical analysis and were the same as for
previously published patient series [26,35] (Table 1).
2.4. Statistical analysis
Statistical analysis was performed using SPSS 15.0
statistical software (SPSS Inc, Chicago, IL). Associations
between BRCA1 expression and clinicopathologic variables
were analyzed using the χ2and Mann-Whitney U tests. The
association of altered BRCA1 expression upon survival was
analyzed initially by Kaplan-Meier plot and log rank test and
also with Cox regression to adjust for other prognostic
indicators in breast cancers. A P value less than .05 was
Of the informative breast carcinoma cases (n = 1482),
260 cases were grade 1, 485 cases were grade 2, and 737 were
grade 3. At the time of the primary diagnosis, 564 (38%)
patients had LN-positive disease (445 cases with one to 3
positive nodes,119cases with4ormorepositive).Recurrence
occurred in 256 cases (17.6%), distant metastases in 158 cases
(10.9%), and 149 (9.7%) patients died from breast cancer. The
patients had a median age of 54 years (range, 18–70 years).
Source, dilution, pretreatment, and cutoff values of antibodies used
Antibody, cloneDilutionSourcePretreatmentCutoff values
ER, clone 1D5
PR, clone PR 636
EGFR, clone EGFR.113
c-erbB3, clone RTJ1
AR, clone F39.4.1
p53, clone DO7
Novocastra, Newcastle, UK
Biogenex, San Ramon, CA
Boehringer Mannheim Biochemica,
South San Francisco, CA
BD Biosciences, San Jose, CA
CK14, clone LL002
Anti–E-cadherin (clone HECD-1)
≥100 (H-score; median)
Anti–P-cadherin (clone 56)
Bcl2, clone 124
Anti-FHIT (clone ZR44)
859Expression of BRCA1 protein in breast cancer
3.1. BRCA1 expression in breast cancer
In the breast, staining was localized to the nuclei of the
parenchymal cells with no cytoplasmic or membranous
staining. In the malignant tissues, unlike normal breast, the
expression intensity was heterogeneous and frequently was
less intense than in normal breast and was detected in both
nuclei and, in some cases, cytoplasm of the malignant cells.
Complete loss of nuclear expression was observed in 223
breast cancer cases (15%). Reduced expression was detected
in 578 (39%), whereas strong immunostaining (H-score
N100) was seen in 681 (46%) breast cancers. Staining was
mainly localized to the nuclei, but unlike normal breast
tissue, the expression intensity was heterogeneous and was
frequently less intense than in normal breast (Figs. 1 and 2).
Cytoplasmic expression was detected in 541 breast cancers
(36.6 %), which was associated with nuclear expression
except in 67 cases (5.1%) that showed cytoplasmic
expression only. The average percentage of BRCA1-positive
cells was 70% (81% in grades 1 and 2, and 58% in grade 3).
BRCA1 stromal staining was weak and insignificant, and,
therefore, it was not considered in the analysis. This may
reflect the size of cores (TMA), their high proportion of
tumor cells or due to genuine weak or absence of expres-
sion of BRCA1 protein in the stroma of the malignant
3.2. Nuclear BRCA1 expression in relation to
Altered BRCA1 expression, either absent or reduced
nuclear expression, was more frequent in ductal carcinomas
of no special type (duct/NST) (66%) and medullary-like
carcinomas (77%) and less frequent in lobular (27%),
mucinous (12%), and tubular mixed carcinomas (χ2= 132.9,
df = 9, P b.001). Complete loss or reduced BRCA1 nuclear
expression was associated with high tumor grade, advanced
LN stage, large tumor size, definite VI, negative hormone
receptors (ER [χ2= 133.4, P b .001], PR [χ2= 112.8, P b
.001], and AR [χ2= 98.6, P b .001]), and positive p53
expression (Table 2). Loss or reduced expression also
showed positive associations with expression of P-cadherin
(χ2= 6.3, P = .04), HER3 (χ2=44.5, P b .001), and HER4
(χ2= 127.8, P b .001), with negative expression of FHIT
protein (χ2= 47.8, P b.001), luminal CKs (7/8 and 19) (χ2=
21.7, P b .001), and MUC-1 protein (χ2= 17.2, P =
Although not significant, loss or reduced BRCA1 nuclear
expression showed a trend for development of recurrence
(χ2= 4.7, P = .09), distant metastasis (χ2= 5.1, P = .07),
and negative Bcl-2 expression (χ2= 3.1, P = .08). No
association was found with breast cancer death rate,
expression of HER1, HER2, neuroendocrine markers
(chromogranin-A and synaptophysin), or p21 expression.
To evaluate the relation between BRCA1 IHC expression
and basal-like class of breast cancer, we assessed its
expression in the different categories used to define basal-
like cancer [36-38]. An association was found between
altered nuclear BRCA1 expression and basal-like cancer as
defined by (i) Nielsen criteria (ER-negative, HER2-negative,
CK5/6-positive, and/or EGFR-positive ), in which 123
cases (76% of basal-like cancer) showed altered BRCA1
nuclear expression (χ2= 31.9, P b .001); (ii) positive basal
CK expression (CK5/6-positive and/or CK14-positive )
(χ2= 14.2, P = .001); (iii) positive CK5/6 and/or EGFR
(χ2= 8.9, P = .009). An association was also found
between altered nuclear BRCA1 expression and triple-
negative phenotype (ER-negative, PR-negative, and HER-
negative) , in which 185 cases (80% of triple-negative
NST) showing strong positive BRCA1 nuclear expression.
A case of invasive duct carcinoma of the breast (duct/
in tumor cells as compared to adjacent, strong positive, normal
A case of duct/NST showing reduced BRCA1 expression
860E. A. Rakha et al.
phenotype) showed altered BRCA1 nuclear expression
(χ2= 68.3, P b.001).
3.3. Cytoplasmic BRCA1 expression
In contrast to nuclear expression, positive rather than
absence of cytoplasmic staining was detected more
frequently in duct/NST and medullary-like carcinomas
and was rarely identified in lobular tumors (χ2= 56, P b
.001). Cytoplasmic expression was also associated with
high grade, large size, development of local recurrence
(χ2= 4.4, P = .036), p53 expression, P-cadherin, EGFR
(χ2= 33.3, P b .001), HER2 (χ2= 14, P b .001), and basal
CKs (χ2= 11.6, P = .001) but not associated with PR, AR, or
the triple-negative phenotype (χ2= 0.2, P = .94). An
association of borderline significance was found between
positive cytoplasmic BRCA1 expression and ER negativity
(χ2= 3.8, P = .05).
Interestingly, when we stratified cases into different
subgroups, we found that in grade 1 tumors (260 cases),
cytoplasmic BRCA1 was associated with larger size (χ2=
4.3, P = .03), development of recurrence (χ2= 4, P = .04)
but no such association was found in grades 2 and 3 tumors.
3.4. Patients’ outcome
Survival analyses revealed an association between nuclear
BRCA1 and DFI (LR = 7, P = .03). The difference was
mainly found between the negative group (which showed
absence of expression) and the other 2 groups (reduced
expression and strong expression) (LR = 8.2, P = .004) with
obvious overlap in the 2 curves presenting the last 2 groups
(LR = 0.5, P = .8) (Fig. 3A). However, no significant
association has been identified in relation to OS in the whole
series (LR = 2.7, P = 0.3) or in the different subgroups
Cytoplasmic BRCA1 expression was inversely associated
with DFI in the whole series (LR = 5.9, P = 0.015) (Fig. 4A).
Cytoplasmic expression also showed an inverse association
with DFI in grade 1 subgroup (LR = 8.2, P = .02), in the
smaller size subgroup (≤1.5 cm) (LR = 7.6, P = .02), in the
LN-negative (LR = 10.3, P = .006), and in the ER-positive
subgroups (LR = 11.9, P = .002), but not in the advanced
and ER-negative subgroups. Moreover, in the ER-positive
subgroup (1012 cases), cytoplasmic BRCA1 was also
inversely associated with OS (LR = 6.3, P = .043) (Fig. 4B).
Associations between nuclear BRCA1 expression and clinicopathologic features in breast cancer
Variables NegativeReduced StrongTotalχ2P value
No% No% No%
861Expression of BRCA1 protein in breast cancer
Multivariate analyses showed that neither nuclear nor
cytoplasmic expression of BRCA1 has an independent
prognostic significance in the whole tumor series with
regard to DFI or OS. However, in grade 1 subgroup,
multivariate analysis with adjustment for other prognostic
factors including tumor size, LN status, VI, and ER
expression showed that cytoplasmic expression of BRCA1
was an independent predictor of DFI (Table 3).
The complex genomic organization of the BRCA1 gene,
the wide array of mutations, the presence of multiple
polymorphisms, and the genetic heterogeneity of breast
cancer imply that rapid screening in a routine diagnostic
setting will be a major technical challenge . Previous
studies have demonstrated that IHC detection of loss of
BRCA1 protein can identify cases associated with BRCA1
disease-free events (Kaplan-Meier method and log-rank test). B,
Correlation between BRCA1 nuclear expression and OS (LR = 2.7,
P = .3).
A, Correlation between BRCA1 nuclear expression and
and disease-free events. B, Correlation between BRCA1 cytoplas-
mic expression and OS in the ER-positive tumors.
A, Correlation between BRCA1 cytoplasmic expression
related to DFI in grade 1 breast cancer
Multivariate Cox regression analyses of factors
(95% CI )
Cytoplasmic BRCA1 expression
1 vs 3
2 vs 3
Tumor size (≥1.5 cm)⁎
⁎Compared with tumor size b1.5 cm.
3.25 (1.38-7.6) .007
862E. A. Rakha et al.
gene mutations with high sensitivity and specificity [11,40].
This study has investigated the expression profile, prognostic
value, and clinical implication of BRCA1 protein expression
in breast carcinomas using IHC. To minimize confounding
variables on the significance of its expression, we have
studied a large and well-characterized series of breast cancer
In breast, strong uniform nuclear expression of BRCA1
was observed in the normal parenchymal tissues. Altered
expression (absent or reduced nuclear expression or
positive cytoplasmic BRCA1 expression) was only found
in the malignant tissues. This observed altered expression
of BRCA1 was associated with other parameters of poor
prognostic and with shorter DFI. In breast cancer, altered
expression was seen more frequently in duct/NST and
medullary-like carcinomas, tumors with poor NPI, devel-
opment of recurrence and distant metastasis, negative
hormone receptor, and positive p53 and P-cadherin
expression. Our results are consistent with previous IHC
and mutation analyses of BRCA1 in breast cancer, which
demonstrated that BRCA1 mutation–positive tumors or
altered expression of BRCA1 was associated with similar
characteristics and with parameters of poor prognosis and
shortened survival [10,14,15,41-45]. However, it is impor-
tant to mention that some studies evaluating BRCA1
protein expression and prognosis have shown different
results. For examples, Taylor et al  noted both nuclear
and cytoplasmic staining in the majority of normal breast
epithelium and lack of correlation between cytoplasmic
staining and clinical features; Fraser et al  showed no
relation to outcome or tumor pathology, however, in their
study; MS110 (the antibody used in the current study)
showed cross reactivity by Western blotting suggesting
There is still an ongoing debate concerning the cellular
localization of BRCA1 protein in breast cancer and the
significance of its abnormal cellular localization. Cytoplas-
mic expression as detected by IHC was documented in
sporadic breast carcinomas and was suggested to play a role
in these tumors [46-48]. Interestingly, we have observed that
cytoplasmic expression of BRCA1 protein in breast cancer,
as detected by the methodology used in this study, is related
to behavior of less aggressive tumor types (low-grade, small-
size, and ER-positive tumors). In these tumors, positive
cytoplasmic expression was associated with other variables
of poor prognosis and showed an inverse association with
survival. For example, in grade 1 tumors, cytoplasmic
BRCA1 expression was an independent predictor of DFI
whereas size and LN stage were not. These results indicate
that BRCA1 dysregulation may also play a role in early well-
differentiated tumors as well as those poorly differentiated,
hormone receptor–negative tumors that are known to be
associated with BRCA1 gene mutation. Our findings are also
supported by (1) the study of Wilson et al  who showed
that among the different splice variants of BRCA1, the
BRCA1-delta 11b, which lacks most of exon 11, was
localized in the cytoplasm instead of the nucleus. They
suggest that this variant and the full-length BRCA1 may
have distinct roles in cell growth regulation and tumorigen-
esis; (2) previous demonstration that different breast tumor
grades have distinct molecular origins, pathogenesis, and
behavior with the presence of distinct genetic differences
between grade I and grade III tumors . Therefore, an
alterative explanation of the presence of cytoplasmic
expression could be production of abnormal BRCA1
protein through specific epigenetic changes or nontrunca-
tion mutations that are different from those identified in
familial cancers. This abnormal protein may play a role in
the development of sporadic breast cancer which is different
from that produced by germline mutation of BRCA1 gene in
the familial cases. However, this point needs further study
to assess the protein and gene status in the tumors which
showed cytoplasmic expression. Moreover, taking into
account that this series is an unselected population of
breast cancer patients with subsequent heterogeneity of
systemic treatments given to individual cases, the result
of correlation with variables of outcome needs to be
interpreted with caution.
There are several lines of evidence to suggest a link
between BRCA1 deficiency and basal-like breast cancer .
Previous studies have demonstrated that many phenotypical,
immunohistochemical, clinical characteristics, and molecu-
lar features are shared by basal-like breast cancers, as defined
by cDNA expression microarrays and tumors that arise in
carriers of BRCA1 germline mutations. The majority of
BRCA1-associated tumors are “triple negative,” express
basal CKs, in addition to other markers commonly seen in
basal-like tumors such as p53 and P-cadherin [43,52-58],
and, in most studies, both patient groups have a poor
outcome [43,59]. To emphasize the relationship between
basal-like tumors and BRCA1, some authors have demon-
strated that the use of basal CK staining in combination with
ER and morphology provides a more accurate predictor of
BRCA1 mutation status than previously available and may
be useful in selecting patients for BRCA1 mutation testing
[51,60,61]. Interestingly, in the current study, an association
between IHC expression of BRCA1 and basal-like tumors,
using different definitions, was found. In addition, 80% of
cases with triple-negative phenotype showed altered nuclear
BRCA1 expression. Similarly, an association between
altered BRCA1 nuclear expression and positive basal CKs
(CK5/6 and/or CK14 ) expression was found. These
findings also support the relationship between basal-like
class of breast cancer and BRCA1 abnormalities and may
emphasize the role of IHC detection of BRCA1 to identify
basal-like cancer in routine practice.
In conclusion, we have confirmed in a large series of
breast cancer cases that aberrant expression in terms of level
of expression and subcellular localization of BRCA1 protein
is related to biological and pathologic prognostic character-
istics as well as clinical outcome. The features of tumors with
altered BRCA1 in our study were similar to those described
863Expression of BRCA1 protein in breast cancer
in previous studies of familial cancers with BRCA1 germline
mutation and showed the same association with other
variables indicating that BRCA1 alteration in sporadic
tumors are more important than previously thought and
confirmed the value of IHC in detection of BRCA1 alteration
in routine practice. Its clinical role in prognostic evaluation
of these tumors merits further investigation.
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