AJCP / Original Article
Immunohistochemical Evaluation of GATA-3 Expression
in ER-Negative Breast Carcinomas
Haiyan Liu, MD,1 Jianhui Shi, MD, PhD,1 Jeffrey W. Prichard, DO,1 Yun Gong, MD, PhD,2
and Fan Lin, MD, PhD1
From 1Geisinger Medical Center, Danville, PA; and 2The University of Texas M.D. Anderson Cancer Center, Houston.
Key Words: ER negative; Breast carcinoma; GATA-3; GCDFP-15; Mammaglobin
Am J Clin Pathol May 2014;141:648-655
CME/SAM
DOI: 10.1309/AJCP0Q9UQTEESLHN
ABSTRACT
Objectives: Estrogen receptor (ER), gross cystic disease
fluid protein 15 (GCDFP-15), and mammaglobin (MGB)
are commonly used breast-specific immunomarkers;
however, about half of metastatic breast carcinomas are
negative for all three. GATA-binding protein 3 (GATA-3)
has emerged recently as a sensitive and relatively specific
immunomarker for breast and urothelial carcinomas, but
the data documenting its expression in ER-negative breast
carcinomas are limited; this often poses a dilemma in
the setting of metastases. The purpose of this study is to
investigate expression of GATA-3 in ER-negative breast
carcinomas.
Methods: Immunohistochemical evaluation of GATA-3,
GCDFP-15, and MGB on 96 ER-negative breast carcinomas
was performed.
Results: Overall, 69% (66/96), 15% (14/96), and 35%
(34/96) of ER-negative breast carcinomas expressed
GATA-3, GCDFP-15, and MGB, respectively.
Conclusions: Our data suggest that GATA-3 is, so far,
the best breast-specific immunomarker, especially when
encountering ER-negative metastatic breast carcinomas.
GATA-3 should be included in the panel of immunomarkers
in the workup of tumors of unknown primary.
648 Am J Clin Pathol 2014;141:648-655
648 DOI: 10.1309/AJCP0Q9UQTEESLHN
Downloaded from http://ajcp.oxfordjournals.org/ at Universitatea de Medicin&#259 on January 20, 2017
Upon completion of this activity you will be able to:
list the immunomarkers commonly used to identify breast primary.
discuss the sensitivity and specificity of each of those
immunomarkers.
apply those immunomarkers in their daily practice.
The ASCP is accredited by the Accreditation Council for Continuing
Medical Education to provide continuing medical education for physicians.
The ASCP designates this journal-based CME activity for a maximum of
1 AMA PRA Category 1 Credit per article. Physicians should claim only
the credit commensurate with the extent of their participation in the activ-
ity. This activity qualifies as an American Board of Pathology Maintenance
of Certification Part II Self-Assessment Module.
The authors of this article and the planning committee members and staff
have no relevant financial relationships with commercial interests to disclose.
Questions appear on p 753. Exam is located at www.ascp.org/ajcpcme.
In current practice, estrogen receptor (ER), gross cystic
disease fluid protein 15 (GCDFP-15), and mammaglobin
A (MGB) serve as breast-specific immunomarkers in the
workup of tumors of unknown primary.1-5 However, the sen-
sitivities for GCDFP-15 and MGB are reported in the ranges
of 35% to 55% and 65% to 70%, respectively. Our unpub-
lished data on tissue microarray (TMA) sections of 250 cases
of invasive breast carcinomas, including ductal, lobular, and
other special types, is even lower: 30% for GCDFP-15 and
50% for MGB, which is similar to the reports by Bhargava
et al,2 who found GCDFP-15 expression in 23.1% and MGB
expression in 55.4% of breast carcinomas, and by Lewis et
al,5 who reported GCDFP-15 labeling of 37% and MGB
labeling of 54% in breast carcinomas. The rate of ER-negative
metastatic breast carcinoma is reported in the range of 40%
to 52%.6-13 Given the frequent absence of expression of cur-
rently available breast-specific immunomarkers (such as ER,
American Society for Clinical Pathology

GCDFP-15, and MGB) in metastatic breast carcinomas, stud-
ies to discover newer breast-specific immunomarkers were
undertaken. NY-BR-1 and GATA-binding protein 3 (GATA-
3) are among the most promising immunomarkers.
NY-BR-1 is a mammary differentiation antigen expressed
in normal mammary tissue and its malignant counterpart, with
a predominantly cytoplasmic staining pattern. Its mRNA
expression on reverse transcriptase polymerase chain reac-
tion is restricted to carcinomas of the breast, testis, and pros-
tate.14-16 Its expression in breast carcinomas was reported as
58.4% by Woodard et al17 and 46.6% by Balafoutas et al18;
however, NY-BR-1 expression is strongly associated with
ER expression in both studies. Its expression in ER-negative
breast carcinomas was reported as much lower, 18% and
28.4%, respectively.
GATA-3 is one of six members of a subfamily of
zinc finger transcription factors, plays an important role in
cell-fate specification, and has recently emerged as a criti-
cal determinant of luminal epithelial cell differentiation in
the adult mammary gland. GATA-3 is highly expressed in
luminal A breast carcinomas.19,20 Previously, we had stud-
ied GATA-3 expression in 1,110 cases of various human
carcinomas and 310 cases of normal tissues using immu-
nohistochemical analysis of TMA sections. We concluded
that GATA-3 is a sensitive and specific marker for breast
and urothelial carcinomas.21 In the current study, we used
immunohistochemical analysis to further investigate the
expression of GATA-3 in 96 ER-negative breast carci-
nomas, including 49 TMA cases and 47 consecutive core
needle biopsy (CNB) specimens. In addition, immunoassays
of GCDFP-15 and MGB were also performed for compari-
son. The aims of this study are to investigate the expression
of GATA-3 in ER-negative breast carcinomas, to compare it
with other breast-specific markers, and ultimately to evalu-
ate its diagnostic usefulness as a breast-specific immuno-
marker in the workup of tumors of unknown primary.
Materials and Methods
Construction of TMA Block
The study was approved by the institutional review board
at Geisinger Medical Center (Danville, PA). Forty-nine cases
of ER-negative primary breast carcinomas, including invasive
ductal carcinoma (IDC) grade 2 (n = 21), IDC grade 3 (n =
22), and others (n = 6, including 2 metaplastic, 2 medullary,
and 2 apocrine carcinomas), were retrieved from the surgi-
cal pathology archives at Geisinger Medical Center from
2000 to 2009. These samples include 39 Her2/neunegative
and 10 Her2/neupositive cases. A TMA block with two
punches of 1.0 mm each for each case was constructed as
American Society for Clinical Pathology
AJCP / Original Article
previously described.22,23 The ER-negative status is defined
by ER immunostaining on TMA sections using the current
guideline (<1%). The tumor grading is based on the Notting-
ham combined histologic grade (Elston-Ellis modification of
Scarff-Bloom-Richardson grading system).
CNB Cases
Forty-seven consecutive ER-negative CNB cases were
retrieved from the archives of the Department of Labora-
tory Medicine at Geisinger Medical Center from 2010 to
2011, including IDC grade 2 (n = 8), IDC grade 3 (n = 30),
metaplastic carcinomas (n = 4), carcinoma with medullary
features (n = 1), and carcinoma with apocrine features (n =
Downloaded from http://ajcp.oxfordjournals.org/ at Universitatea de Medicin&#259 on January 20, 2017
4). Thirty-seven cases were Her2/neu negative and 10 were
Her2/neu positive.
Immunohistochemical Analysis
Immunohistochemical analysis was performed to study
GATA-3 (Biocare Medical, Concord, CA), GCDFP-15 (Cell
Marque Corp, Rocklin, CA), and MGB (Ventana Medical
Systems, Tucson, AZ) expression in 49 TMA and 47 CNB
specimens of ER-negative breast carcinomas. The Dako
staining system (1:25 dilution, ethylenediaminetetraacetic
acid antigen retrieval, and 45-minute incubation for primary
antibody; Dako, Carpinteria, CA) was used as described pre-
viously.24,25 The staining intensity was graded as weak or
strong. The distribution for GATA-3 was recorded as negative
(<5% of tumor cell nuclei stained), 1+ (5%-25%), 2+ (26%-
50%), 3+ (51%-75%), or 4+ (>75%); for MGB and GCDFP-
15, any cytoplasmic staining was defined as positive. Two
surgical pathologists (H.L. and F.L.) independently evaluated
the immunostained slides. Any discrepancies between the
staining results of the two pathologists were resolved by dis-
cussion at a multihead microscope.
Results
GATA-3 Expression in 96 ER-Negative Breast
Carcinomas
GATA-3 expression was demonstrated in 69% (66/96)
of ER-negative breast carcinomas, including 59% (29/49) of
TMA and 79% (37/47) of CNB cases. The majority of GATA-
3positive cases (73%) showed a strong and diffuse (4+ or
3+) nuclear staining pattern Image 1A and Image 1B. Of
the six metaplastic carcinomas, only one (17%) showed weak
2+ staining Image 1C and Image 1D. Similarly, one of the
three (33%) carcinomas with medullary features showed weak
2+ staining Image 1E and Image 1F. The six cases of apo-
crine carcinomas revealed a heterogeneous staining pattern,
from nonreactive (one case) to strong, diffuse, or weak focal
Am J Clin Pathol 2014;141:648-655 649
649 DOI: 10.1309/AJCP0Q9UQTEESLHN 649
Liu et al / GATA-3 Expression in ER-Negative Breast Carcinomas

A B

Downloaded from http://ajcp.oxfordjournals.org/ at Universitatea de Medicin&#259 on January 20, 2017

C D

E F

Image 1 A, Estrogen receptornegative invasive ductal carcinoma of the breast, grade 3 (H&E, 400). B, GATA-binding protein
3 (GATA-3) nuclear staining; the majority of positive cases show strong and diffuse (4+ or 3+) nuclear staining (400). C, Invasive
metaplastic carcinoma of the breast (H&E, 400). D, Five (83%) of six metaplastic carcinomas are negative for GATA-3; only one case
is GATA-3 positive, showing weak 2+ nuclear staining (400). E, Invasive ductal carcinoma of the breast with medullary features
(H&E, 400). F, One of the three carcinomas with medullary features is GATA-3 positive, showing weak 2+ nuclear staining (400).

650 Am J Clin Pathol 2014;141:648-655 American Society for Clinical Pathology

650 DOI: 10.1309/AJCP0Q9UQTEESLHN
 AJCP / Original Article

staining patterns Image 2 . The GATA-3 staining results for
96 ER-negative breast carcinomas are summarized in Table
1, with staining intensity for TMA shown in Table 2 and
for CNB in Table 3.
MGB Expression in 96 ER-Negative Breast Carcinomas
MGB expression was demonstrated in 35% (34/96) of
ER-negative breast carcinomas, including 37% (18/49) of
TMA and 34% (16/47) of CNB cases. Of the six metaplastic
carcinomas, only one (17%) showed strong 1+ cytoplasmic
staining. All three carcinomas with medullary features and
the six apocrine carcinomas were nonreactive. The MGB
immunostaining results for 96 ER-negative breast carcinomas
are summarized in Table 4.
GCDFP-15 Expression in 96 ER-Negative Breast
Carcinomas
GCDFP-15 expression was demonstrated in 15% (14/96)
of ER-negative breast carcinomas, including 12% (6/49) of
TMA and 17% (8/47) of CNB cases; 83% (5/6) of apocrine car-
cinomas expressed GCDFP-15 (Image 2D). The six metaplastic
carcinomas and three carcinomas with medullary features were
all nonreactive. The GCDFP-15 immunostaining results for 96
ER-negative breast carcinomas are summarized in Table 5.

Downloaded from http://ajcp.oxfordjournals.org/ at Universitatea de Medicin&#259 on January 20, 2017

A B

C D

Image 2 A, Invasive ductal carcinoma of the breast, apocrine type (H&E, 400). Three (75%) of four apocrine carcinomas
are GATA-binding protein 3 (GATA-3) positive, showing heterogeneous patterns, from strong 4+ (B, 400) to weak 2+ nuclear
staining (C, 400). D, Gross cystic disease fluid protein 15 (GCDFP-15) is expressed in five (83%) of six apocrine carcinomas
(200).

American Society for Clinical Pathology Am J Clin Pathol 2014;141:648-655 651

651 DOI: 10.1309/AJCP0Q9UQTEESLHN 651
Liu et al / GATA-3 Expression in ER-Negative Breast Carcinomas

Table 1
Expression of GATA-3 in 96 Cases of ER-Negative Breast CAs

GATA-3 Expression, TMA GATA-3 Expression, CNB

Tumor Type No. of Cases No. (%) of Positive Cases No. of Cases No. (%) of Positive Cases

IDC, G2 21 13 (62) 8 7 (88)

IDC, G3 22 15 (68) 30 24 (80)
IDC, HG, metaplastic 2 0 (0) 4 1 (25)
IDC, HG, medullary 2 0 (0) 1 1 (100)
IDC, apocrine features 2 1 (50) 4 4 (100)
Total 49 29 (59) 47 37 (79)

CA, carcinoma; CNB, core needle biopsy; ER, estrogen receptor; G, grade; GATA-3, GATA-binding protein 3; HG, high-grade; IDC, invasive ductal carcinoma; TMA, tissue
microarray.

Downloaded from http://ajcp.oxfordjournals.org/ at Universitatea de Medicin&#259 on January 20, 2017

Table 2
GATA-3 Expression in TMA Cases

No. of Positive Specimens

Strong Staining Weak Staining

No. of Negative
Tumor Type Specimens 4+ 3+ 2+ 1+ 4+ 3+ 2+ 1+

IDC, G2 (N = 21) 8 10 2 0 0 0 1 0 0
IDC, G3 (N = 22) 7 6 5 1 0 0 1 1 1
IDC, HG, metaplastic (N = 2) 2 0 0 0 0 0 0 0 0
IDC, HG, medullary (N = 2) 2 0 0 0 0 0 0 0 0
IDC, apocrine features (N = 2) 1 0 0 0 0 0 0 1 0

G, grade; GATA-3, GATA-binding protein 3; HG, high-grade; IDC, invasive ductal carcinoma; TMA, tissue microarray.

Table 3
GATA-3 Expression in Core Needle Biopsy Cases

No. of Positive Specimens

Strong Staining Weak Staining
No. of Negative
Tumor Type Specimens 4+ 3+ 2+ 1+ 4+ 3+ 2+ 1+

IDC, G2 (N = 8) 1 6 0 1 0 0 0 0 0
IDC, G3 (N = 30) 6 14 3 2 1 0 2 2 0
IDC, HG, metaplastic (N = 4) 3 0 0 0 0 0 0 1 0
IDC, HG, medullary (N = 1) 0 0 0 0 0 0 0 1 0
IDC, apocrine features (N = 4) 0 1 1 0 0 0 1 1 0

G, grade; GATA-3, GATA-binding protein 3; HG, high-grade; IDC, invasive ductal carcinoma.

Table 4
Expression of MGB in 96 Cases of ER-Negative Breast CAs

MGB Expression, TMA MGB Expression, CNB

Tumor Type No. of Cases No. (%) of Positive Cases No. of Cases No. (%) of Positive Cases

IDC, G2 21 9 (43) 8 4 (50)

IDC, G3 22 8 (36) 30 8 (27)
IDC, HG, metaplastic 2 0 4 1 (25)
IDC, HG, medullary 2 0 1 0
IDC, apocrine features 2 1 (50) 4 3 (75)
Total 49 18 (37) 47 16 (34)

CA, carcinoma; CNB, core needle biopsy; ER, estrogen receptor; G, grade; HG, high-grade; IDC, invasive ductal carcinoma; MGB, mammaglobin; TMA, tissue microarray.

652 Am J Clin Pathol 2014;141:648-655 American Society for Clinical Pathology

652 DOI: 10.1309/AJCP0Q9UQTEESLHN
 AJCP / Original Article

Table 5
Expression of GCDFP-15 in 96 Cases of ER-Negative Breast CAs

GCDFP-15 Expression, TMA GCDFP-15 Expression, CNB

Tumor Type No. of Cases No. (%) of Positive Cases No. of Cases No. (%) of Positive Cases

IDC, G2 21 2 (10) 8 2 (25)

IDC, G3 22 2 (9) 30 3 (10)
IDC, HG, metaplastic 2 0 4 0
IDC, HG, medullary 2 0 1 0
IDC, apocrine features 2 2 (100) 4 3 (75)
Total 49 6 (12) 47 8 (17)

CA, carcinoma; CNB, core needle biopsy; ER, estrogen receptor; G, grade; GCDFP-15, gross cystic disease fluid protein 15; HG, high-grade; IDC, invasive ductal carcinoma;
TMA, tissue microarray.

Downloaded from http://ajcp.oxfordjournals.org/ at Universitatea de Medicin&#259 on January 20, 2017

Discussion
Identifying metastatic breast carcinoma of primary ori-
gin can be challenging, especially with ER-negative tumors,
which have been reported in nearly half of all metastatic breast
carcinomas. In addition to ER, the currently available breast-
specific immunomarkers, such as GCDFP-15 and MGB, are
usually not expressed in high-grade breast carcinomas, such
as basal-like and triple-negative carcinomas.26,27 The newer
immunomarker, NY-BR-1, was reported to be expressed in
18% and 28.4% of ER-negative breast carcinomas as stated
earlier. GATA-3 is emerging as a sensitive and relatively spe-
cific marker for breast carcinomas. Several studies reported its
high expression in breast and urothelial carcinomas,28-31 but
its expression in salivary gland tumors and autonomic nervous
system tumors was also reported recently.32,33 In our previous
study, GATA-3 expression was identified in 94% of invasive
breast carcinomas (comprising ER-positive and ER-negative
cases) and 86% of urothelial carcinomas. However, only a
few reports in the literature have explored the expression of
GATA-3 in ER-negative tumors, which, indeed, are the most
problematic cases in terms of defining breast primary in set-
tings of metastases. For ER-negative breast carcinomas, Yang
and Nonaka34 reported that 6.7% (2/30) and Albergaria et
al35 reported that 17.6% (16/91) expressed GATA-3; Cimino-
Mathews et al36 found that GATA-3 was expressed in 54%
of ER-negative tumors, including 86% of Her2-type, 43% of
triple-negative, and 54% of metaplastic carcinomas.
To further investigate the expression of GATA-3 in
ER-negative tumors, we conducted an immunohistochemical
investigation of GATA-3 expression in 96 ER-negative breast
carcinomas. Our study revealed that an overall 69% (66/96) of
ER-negative breast carcinomas expressed GATA-3, including
59% (29/49) of TMA and 79% (37/47) of CNB cases. Our
data are similar to those of Cimino-Mathews et al36: 59% of
TMAs in our data compared with their 54% positive rate in
TMA cases. Our CNB cases showed a higher expression rate
of 79%, which more closely approximates the daily practice of
tissue sections. Moreover, the majority of GATA-3positive
cases showed a diffuse and strong nuclear staining pattern,
which is significant and can be reliably interpreted. Metaplas-
tic carcinomas and carcinomas with medullary features tended
to lack or have markedly decreased GATA-3 expression
in our study; however, the number of cases studied is very
limited. Cimino-Mathews et al36 reported that 54% (7/13) of
metaplastic carcinomas expressed GATA-3, but the staining
was weak, and nearly half of the positive cases showed only
1+ staining. The small number of metaplastic carcinomas may
contribute to the lower positive rate in our study; however, the
expression of GATA-3 in metaplastic and medullary carcino-
mas needs to be validated in larger studies.
In contrast, the expression of GCDFP-15 and MGB in
ER-negative breast carcinomas was 15% (14/96) and 35%
(34/96), respectively, in our current study. Among the 14
cases of GCDFP-15positive tumors, five were apocrine
carcinomas. These data revealed a limited use for GCDFP-
15 in the difficult workup of tumors of unknown primary,
which are often ER-negative metastases. MGB showed a
35% rate of expression, which is higher than that of GCDFP-
15 but still expressing a sensitivity that is relatively low. In
addition, MGB is not breast specific. It had been reported
in 50% to 66% of gynecologic malignancies,37-39 similar
to our previous study, in which 64% (82/128) of endome-
trial adenocarcinomas on TMA sections expressed MGB.40
When dealing with challenging cases, especially in female
patients, the differential diagnosis between breast and gyne-
cologic malignancies often arises. The expression of MGB
in both tumors makes it less useful in differentiating breast
vs gynecologic malignancies. On the other hand, GATA-3 is
highly expressed in breast carcinomas, as stated earlier, and
expressed only in 2% (2/96) of the endometrial carcinomas
and in none of the ovarian serous carcinomas (n = 56) and
endocervical adenocarcinomas (n = 17).21 Compared with
the 69% positive rate for GATA-3 in ER-negative tumors
and with the majority of positive cases having a diffuse and
strong staining pattern, we concluded that GATA-3 is a more
sensitive immunomarker for breast primary.

American Society for Clinical Pathology Am J Clin Pathol 2014;141:648-655 653

653 DOI: 10.1309/AJCP0Q9UQTEESLHN 653
Liu et al / GATA-3 Expression in ER-Negative Breast Carcinomas
Our data, in conjunction with our previous findings of
GATA-3 expression in 94% of breast carcinomas and 86%
of urothelial carcinomas, demonstrated that GATA-3 is by far
the best breast-specific immunomarker. With this relatively
high sensitivity and specificity, GATA-3 should be included
in the panel of immunomarkers in the workup of tumors of
unknown origin.
Address reprint requests to Dr Liu: Dept of Laboratory Medicine,
MC 01-31, Geisinger Medical Center, 100 N Academy Ave,
Danville, PA 17822; hliu1@geisinger.edu.
Acknowledgments: The authors thank Tina Brosious and Erin
Powell for construction of TMA blocks and cutting TMA sections,
Angie Bitting for assistance with immunostains, and Kathy
Fenstermacher for editing the manuscript.
References
1. Watson MA, Fleming TP. Mammaglobin, a mammary-
specific member of the uteroglobin gene family, is
overexpressed in human breast cancer. Cancer Res.
1996;56:860-865.
2. Bhargava R, Beriwal S, Dabbs DJ. Mammaglobin vs GCDFP-
15: an immunohistologic validation survey for sensitivity and
specificity. Am J Clin Pathol. 2007;127:103-113.
3. Chia SY, Thike AA, Cheok PY, et al. Utility of
mammaglobin and gross cystic disease fluid protein-15
(GCDFP-15) in confirming a breast origin for recurrent
tumors. Breast. 2010;19:355-359.
4. Rollins-Raval M, Chivukula M, Tseng GC, et al. An
immunohistochemical panel to differentiate metastatic breast
carcinoma to skin from primary sweat gland carcinomas
with a review of the literature. Arch Pathol Lab Med.
2011;135:975-983.
5. Lewis GH, Subhawong AP, Nassar H, et al. Relationship
between molecular subtype of invasive breast carcinoma
and expression of gross cystic disease fluid protein 15 and
mammaglobin. Am J Clin Pathol. 2011;135:587-591.
6. Gomez-Fernandez C, Daneshbod Y, Nassiri M, et al.
Immunohistochemically determined estrogen receptor
phenotype remains stable in recurrent and metastatic breast
cancer. Am J Clin Pathol. 2008;130:879-882.
7. Idirisinghe PK, Thike AA, Cheok PY, et al. Hormone
receptor and c-ERBB2 status in distant metastatic and locally
recurrent breast cancer: pathologic correlations and clinical
significance. Am J Clin Pathol. 2010;133:416-429.
8. Broom RJ, Tang PA, Simmons C, et al. Changes in estrogen
receptor, progesterone receptor and Her-2/neu status with
time: discordance rates between primary and metastatic
breast cancer. Anticancer Res. 2009;29:1557-1562.
9. Finn RS, Press MF, Dering J, et al. Estrogen receptor,
progesterone receptor, human epidermal growth factor
receptor 2 (HER2), and epidermal growth factor receptor
expression and benefit from lapatinib in a randomized trial of
paclitaxel with lapatinib or placebo as first-line treatment in
HER2-negative or unknown metastatic breast cancer. J Clin
Oncol. 2009;27:3908-3915.
10. Monaco SE, Wu Y, Teot LA, et al. Assessment of estrogen
receptor (ER), progesterone receptor (PR), and human
epidermal growth factor receptor 2 (HER2) status in the
fine needle aspirates of metastatic breast carcinomas. Diagn
Cytopathol. 2013;41:308-315.
654 Am J Clin Pathol 2014;141:648-655
654 DOI: 10.1309/AJCP0Q9UQTEESLHN
11. St Romain P, Madan R, Tawfik OW, et al. Organotropism
and prognostic marker discordance in distant metastases of
breast carcinoma: fact or fiction? a clinicopathologic analysis.
Hum Pathol. 2012;43:398-404.
12. Aitken SJ, Thomas JS, Langdon SP, et al. Quantitative
analysis of changes in ER, PR and HER2 expression in
primary breast cancer and paired nodal metastases. Ann
Oncol. 2010;21:1254-1261.
13. Chang HJ, Han SW, Oh DY et al. Discordant human
epidermal growth factor receptor 2 and hormone receptor
status in primary and metastatic breast cancer and response to
trastuzumab. Jpn J Clin Oncol. 2011;41:593-599.
14. Theurillat JP, Zrrer-Hrdi U, Varga Z, et al. Distinct
expression patterns of the immunogenic differentiation
antigen NY-BR-1 in normal breast, testis and their malignant
counterparts. Int J Cancer. 2008;122:1585-1591.
Downloaded from http://ajcp.oxfordjournals.org/ at Universitatea de Medicin&#259 on January 20, 2017
15. Jger D, Filonenko V, Gout I, et al. NY-BR-1 is a
differentiation antigen of the mammary gland. Appl
Immunohistochem Mol Morphol. 2007;15:77-83.
16. Varga Z, Theurillat JP, Filonenko V, et al. Preferential
nuclear and cytoplasmic NY-BR-1 protein expression in
primary breast cancer and lymph node metastases. Clin
Cancer Res. 2006;12:2745-2751.
17. Woodard AH, Yu J, Dabbs DJ, et al. NY-BR-1 and PAX8
immunoreactivity in breast, gynecologic tract, and other
CK7+ carcinomas: potential use for determining site of
origin. Am J Clin Pathol. 2011;13:428-435.
18. Balafoutas D, Hausen AZ, Mayer S, et al. Cancer testis
antigens and NY-BR-1 expression in primary breast cancer:
prognostic and therapeutic implications. BMC Cancer.
2013;13:271.
19. Burch JB. Regulation of GATA gene expression during
vertebrate development. Semin Cell Dev Biol. 2005;16:71-81.
20. Zheng R, Blobel GA. GATA transcription factors and
cancer. Genes Cancer. 2010;1:1178-1188.
21. Liu H, Shi J, Wilkerson ML, et al. Immunohistochemical
evaluation of GATA3 expression in tumors and normal
tissues: a useful immunomarker for breast and urothelial
carcinomas. Am J Clin Pathol. 2012;138:57-64.
22. Lin F, Zhang PL, Yang XJ, et al. Human kidney injury
molecule-1 (hKIM-1): a useful immunohistochemical marker
for diagnosing renal cell carcinoma and ovarian clear cell
carcinoma. Am J Surg Pathol. 2007;31:371-381.
23. Wilkerson ML, Powell E. Tissue microarray. In: Lin
F, Prichard J, Liu H, et al., eds. Handbook of Practical
Immunohistochemistry: Frequently Asked Questions. New York,
NY: Springer; 2011:45-54.
24. Lin F, Shi J, Liu H, et al. Diagnostic utility of S100P and
von Hippel-Lindau gene product (pVHL) in pancreatic
adenocarcinoma with implication of their roles in early
tumorigenesis. Am J Surg Pathol. 2008;32:78-91.
25. Lin F, Shi J, Liu H, et al. Immunohistochemical detection
of the von Hippel-Lindau gene product (pVHL) in human
tissues and tumors: a diagnostic marker for metastatic renal
cell carcinoma and clear cell carcinoma of the ovary and
uterus. Am J Clin Pathol. 2008;129:592-605.
26. Lewis GH, Subhawong AP, Nassar H, et al. Relationship
between molecular subtype of invasive breast carcinoma
and expression of gross cystic disease fluid protein 15 and
mammaglobin. Am J Clin Pathol. 2011;135:587-591.
27. Huo L, Zhang J, Gilcrease MZ, et al. Gross cystic disease fluid
protein-15 and mammaglobin A expression determined by
immunohistochemistry is of limited utility in triple-negative
breast cancer. Histopathology. 2013;62:267-274.
American Society for Clinical Pathology

28. Higgins JP, Kaygusuz G, Wang L, et al. Placental S100
(S100P) and GATA3: markers for transitional epithelium
and urothelial carcinoma discovered by complementary DNA
microarray. Am J Surg Pathol. 2007;31:673-680.
29. Gruver AM, Amin MB, Luthringer DJ, et al. Selective
immunohistochemical markers to distinguish between
metastatic high-grade urothelial carcinoma and primary
poorly differentiated invasive squamous cell carcinoma of the
lung. Arch Pathol Lab Med. 2012;136:1339-1346.
30. Chang A, Amin A, Gabrielson E, et al. Utility of GATA3
immunohistochemistry in differentiating urothelial
carcinoma from prostate adenocarcinoma and squamous cell
carcinomas of the uterine cervix, anus, and lung. Am J Surg
Pathol. 2012;36:1472-1476.
31. Gulmann C, Paner GP, Parakh RS, et al.
Immunohistochemical profile to distinguish urothelial from
squamous differentiation in carcinomas of urothelial tract.
Hum Pathol. 2013;44:164-172.
32. Schwartz LE, Westra WH, Bishop JA. GATA3
Immunohistochemical expression in salivary gland
neoplasms. Mod Pathol. 2013;26 (S2):311-315.
33. Nonaka D, Wang BY, Sun C-CJ. A study of Phox2b and
GATA3 expression in tumors of autonomic nervous system
derivation. Mod Pathol. 2013;26(S2):136A.
34. Yang M, Nonaka D. A study of immunohistochemical
differential expression in pulmonary and mammary
carcinomas. Mod Pathol. 2010;23:654-661.
American Society for Clinical Pathology
AJCP / Original Article
35. Albergaria A, Paredes J, Sousa B, et al. Expression of FOXA1
and GATA-3 in breast cancer: the prognostic significance
in hormone receptor-negative tumours. Breast Cancer Res.
2009;11:R40.
36. Cimino-Mathews A, Subhawong AP, Illei PB, et al. GATA3
expression in breast carcinoma: utility in triple-negative,
sarcomatoid, and metastatic carcinomas. Hum Pathol.
2013;44:1341-1349.
37. Hagemann IS, Pfeifer JD, Cao D. Mammaglobin expression
in gynecologic adenocarcinomas. Hum Pathol. 2013;44:628-
635.
38. Onuma K, Dabbs DJ, Bhargava R. Mammaglobin expression
in the female genital tract: immunohistochemical analysis
in benign and neoplastic endocervix and endometrium. Int J
Gynecol Pathol. 2008;27:418-425.
39. Classen-Linke I, Moss S, Grting K, et al. Mammaglobin
Downloaded from http://ajcp.oxfordjournals.org/ at Universitatea de Medicin&#259 on January 20, 2017
1: not only a breast-specific and tumour-specific marker,
but also a hormone-responsive endometrial protein.
Histopathology. 2012;61:955-965.
40. Liu H, Yin H, Wang H, et al. Re-evaluation of
immunohistochemical markers in endometrial
adenocarcinomas. Mod Pathol. 2012;25(S2):283A.
Am J Clin Pathol 2014;141:648-655 655
655 DOI: 10.1309/AJCP0Q9UQTEESLHN 655