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reviewed, and none showed statistical signifi cance with low/absent HER2-neu expression were characteristically
an increased risk of subsequent DCIS, although the seen in our ER(+) DCIS groups, similar to previously
index DCIS lesions with high nuclear grade, which had described in IC. While there is a statistically signifi cant
[23]
positive or uncertain margins showed a higher rate of lower expression of GATA-3 in the ER(-) cases, nearly
recurrence. all maintained expression. A signifi cant number of
ER(-) DCIS cases showed FOXA1 expression. FOXA1
We are reporting the results of biological markers and GATA-3 transcription factors have been shown to
expression in terms of recurrence and ER status. ER(-) correlate highly with the luminal A molecular subtype
DCIS with and without recurrence had lower expression of IC. [10,11] Within the luminal, a subtype of IC, it has
of GATA-3 (P < 0.05) than ER(+) cases. A strong HER2 been shown that FOXA1 [10,11] and GATA-3 [22,24] can
overexpression (P < 0.05) and higher proliferation index sub-classify patients into a low and high-risk groups
of Ki-67 (P < 0.05) were seen in ER(-) group. FOXA1 based on their strong expression. FOXA1 via its actions
as an individual biomarker expressed in ER(+) and on the p27 promoter, [16,17] is thought to maintain IC in
ER(-) groups was not statistically signifi cant. Nearly all a less proliferative state, with a decreased metastatic
ER(-) cases retained expression of FOXA1 and GATA-3. potential, [10-13] while GATA-3 is important in the
Overall, cases with recurrence demonstrated the greater maintenance of tumor differentiation and suppression of
percentage of ER(-), HER2 overexpression, and high metastatic potential. Therefore, it is not surprising that
[21]
proliferation compared to nonrecurrence cases [Table 3 these transcription factors are highly expressed in DCIS
and Figure 2].
as well, which by defi nition is an in situ (noninvasive)
Discussion carcinoma.

This is one of the fi rst studies to analyze novel transcription
factors in DCIS patients, and we show that FOXA1 and
GATA-3 expression is strongly seen in both ER(-) and
ER(+) DCIS groups. We observed that strong expression
of FOXA1 and GATA-3, low/intermediate Ki-67, and

a c e

b d f
Figure 2: Representative high grade ductal carcinoma in situ case (×40).
Figure 1: Pathway describing the role of GATA-3 and FOXA1 in development (a and b) Hematoxylin and eosin stain; (c) GATA-3 expression (H score 162); (d)
and maintenance of mammary luminal cells. GATA-3 promoter of FOXA1 FOXA1 expression (H score 180); (e) human epidermal growth factor receptor
transcription which in turn is responsible for expression of ERα regulated 2/neu expression (immunohistochemistry score 3+); (f) Ki-67 expression (15%
genes. FOXA1: Forkhead-box A1; GATA-3: GATA binding protein 3 proliferation rate). FOXA1: Forkhead-box A1; GATA-3: GATA binding protein 3

Table 3: Biomarker score in DCIS, stratifi ed by hormone status and follow up outcome
n (%) ER score PR score P GATA-3 P FOXA1 P HER2 P Ki 67 P
Recurrence DCIS
ER(-) 6 (46) 1 1 0.019* 150 0.12 169 0.50 3 0.032* 35 0.11
ER(+) 7 (54) 150 96 190 169 1 19
Recurrence IC
ER(-) 4 (31) 0 0 0.034* 165 0.021* 192 0.08 2 0.14 16 0.31
ER(+) 9 (69) 182 75 212 216 1 20
No recurrence DCIS
ER(-) 34 (23) 1 6 < 0.001* 158 < 0.001* 178 0.026* 3 < 0.001* 29 < 0.001*
ER(+) 113 (77) 208 96 204 195 1 16
No recurrence IC
ER(-) 11 (24) 0 1 < 0.001* 172 0.019* 223 0.255 3 < 0.001* 47 < 0.01*
ER(+) 35 (76) 197 92 228 211 2 26
ER(-) represents H score < 10, ER(+) represents H score >10. *P value with statistical signifi cance. ER: Estrogen receptor; PR: Progesterone
receptor; DCIS: Ductal carcinoma in situ; IC: Invasive carcinoma; FOXA1: Forkhead-box A1; GATA-3: GATA binding protein 3

Journal of Cancer Metastasis and Treatment ¦ Volume 1 ¦ Issue 2 ¦ July 15, 2015 ¦ 87