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Original Article

Prognostic signifi cance of transcription factors FOXA1 and GATA-3 in
ductal carcinoma in situ in terms of recurrence and estrogen receptor
status

Mamatha Chivukula , Jennifer Picarsic , Gautam Bulusu , Adam Brufsky , Gretchen Ahrendt , Gloria Carter 4
2
3
1
1
2
1 Department of Pathology, Mills-Peninsula Helath Services, Dorothy Schneider Breast Cancer Center, Burlingame, CA 94050, USA.
2 Department of Pathology, Magee-Women’s Hospital of UPMC, Pittsburgh, PA 15213, USA.
3 Department of Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15232, USA.
4 Department of Surgery, Magee-Women’s Hospital of UPMC, Pittsburgh, PA 15213, USA.
Correspondence to: Dr. Mamatha Chivukula, Department of Pathology, Mills-Peninsula Helath Services, Dorothy Schneider Breast Cancer Center,
Burlingame, CA 94050, USA. E-mail: mchivukula@ppmgpath.com
ABSTRACT

Aim: The aim was to analyze the expression of novel biological transcription markers, forkhead-box A1 (FOXA1), GATA binding
protein 3 (GATA-3), and established markers such as Ki-67 (MIB-1) and human epidermal growth factor receptor 2 (HER2) in
estrogen receptor (ER(+)) and ER(-) ductal carcinoma in situ (DCIS) patients with/without recurrence. Methods: Two hundred and
ninety-one cases of DCIS were retrieved from our pathology database, with complete data available for 219 cases. The follow-up
period is from 1988 to 2009. Recurrence is defi ned in terms of DCIS or invasive carcinoma (IC). No recurrence was seen in
88% (196/219) of cases; 12% (26/219) had a recurrence (IC: 13, DCIS: 13). We are reporting the results of biological marker
expression in terms of recurrence and ER status. Results: Our study demonstrates strong expression of GATA-3 in the ER(+) DCIS
in recurrence and nonrecurrence groups similar to previously described in IC. A reduced expression of GATA-3 was observed in
ER(-) recurrence and nonrecurrence groups. A strong HER2 protein expression, as well as high proliferation index, was seen in
recurrence group (DCIS and IC). FOXA1 expression is reduced across the groups though not statistically signifi cant. Conclusion:
This is the fi rst study to analyze novel transcription markers FOXA1 and GATA-3 in DCIS. Further work needs to be done on
a larger cohort of DCIS cases with recurrence to better understand, which variables are best able to predict recurrence and guide
therapy decision strategies. Maintenance of FOXA1 and GATA-3 expression in ER(-) DCIS may offer new promising targets for
therapy in future.
Key words: Ductal carcinoma in situ, estrogen receptor, forkhead-box A1, GATA binding protein 3

Introduction receptor 2 (HER2)-like, basal-like), which confer
prognostic clinical signifi cance, to date few studies have
Ductal carcinoma in situ (DCIS) is a heterogeneous attempted to classify DCIS into similar molecular-based
pre-invasive carcinoma and has become a signifi cant subtypes . [4-6] There is emerging evidence on limited data
proportion of screen-detected breast malignancies in to suggest cDNA microarray, gene-expression profi les can
North American and Western Europe, since the onset of segregate DCIS into similar distinct molecular subtypes as
wide-spread screening mammography nearly two decades in IC; however, a signifi cant proportion of DCIS shows
[4]
ago. [1,2] Unlike invasive breast carcinoma (IC), DCIS is a tumor heterogeneity [4,5,7] making it diffi cult to stratify
more heterogeneous malignancy without clear prognostic DCIS cases into a single subtype, and thus subsequently
indicators for recurrence, defi ned as either recurrent DCIS diminishing the prognostic signifi cance of these molecular
or IC. While the Van Nuys Prognostic Index, based on subtypes, as compared to IC.
histopathologic indicators (high nuclear grade, necrosis,
margin width, and size) has been used clinically for Estrogen receptor (ER) status has been the leading candidate
predicting recurrence, there has been no good biomarker(s) biomarker in DCIS, as it plays a key role in development
that predicts outcome in DCIS. [3] Furthermore, and infl uences hormonal treatment in IC patients. Absence
whereas IC has been classifi ed into distinct molecular of ER was shown to be one of the signifi cant predictors of
[8]
subtypes (luminal A/B, human epidermal growth factor recurrence in IC. In addition, it is well-known that about
30% of ER(+) tumors are not hormone responsive, and
Access this article online about 5-15% of ER(-) tumors are responsive to anti-estrogen
[9]
Quick Response Code: therapy. However, the two broad groups of IC namely
Website: ER(+) and ER(-), are yet to be well understood in DCIS.
www.jcmtjournal.com
Recently, various research groups have looked at
the functional interaction between the forkhead-box
DOI:
10.4103/2394-4722.157600 A1 (FOXA1) winged helix transcription factor and GATA
binding protein 3 (GATA-3), a zinc fi nger transcription

84 Journal of Cancer Metastasis and Treatment ¦ Volume 1 ¦ Issue 2 ¦ July 15, 2015 ¦