Abstract
BackgroundCytokeratin 7 (CK7) and GATA binding protein 3 (GATA3) are considered as immunohistochemical hallmarks of breast cancers; however, there are breast tumors lacking these markers. Clinicopathological characterization of CK7 negative breast cancer has not been addressed previously and similar studies on GATA3 negative tumors are limited.MethodsThis study included 196 consecutive cases of Nottingham Grade 3 breast cancers with 159 cases of Grade 1 and Grade 2 tumors for comparison. CK7 and GATA3 expression was correlated with patient’s age, histological type, pathological grade and stage, hormone receptor status, molecular subtype and overall survival.ResultsCK7 negativity was seen in 13% of Grade 3, 9% of Grade 2, and 2% of Grade 1 cases (P = 0.0457). Similarly, 28% of Grade 3, 5% of Grade 2 and 2% of Grade 1 cases were GATA3 negative (P < 0.0001). CK7 negative tumors did not show association with other clinicopathological parameters. GATA3 negative tumors were enriched in the basal-like molecular subgroup and were associated with negative estrogen receptor (ER) and negative progesterone receptor (PR) statuses. Both CK7 and GATA3 expression showed no association with overall survival in patients with Grade 3 tumor.ConclusionsThis is the first study to characterize CK7 negative breast tumors in the context of clinicopathology. Profiling the CK7 negative and GATA3 negative breast cancers helps to understand the biology of these specific tumor subgroups and may aid in their diagnosis.
Highlights
Cytokeratin 7 (CK7) and GATA binding protein 3 (GATA3) are considered as immunohistochemical hallmarks of breast cancers; there are breast tumors lacking these markers
Thirteen percent (13%) of Nottingham Grade 3 (G3) tumors were negative for CK7, while the negative rates were 9 and 2% for Grade 2 and Grade 1 tumors, respectively (P = 0.0457) (Table 1)
The distribution of CK7 negative tumors in ductal cancers was not associated with tumor grade (P = 0.7565), while more GATA3 negative tumors occurred in Grade 3 ductal cancers than those in Grade 1 and Grade 2 tumors, 27% vs. 6% (P < 0.0001) (Table 3)
Summary
Cytokeratin 7 (CK7) and GATA binding protein 3 (GATA3) are considered as immunohistochemical hallmarks of breast cancers; there are breast tumors lacking these markers. Clinicopathological characterization of CK7 negative breast cancer has not been addressed previously and similar studies on GATA3 negative tumors are limited. Cytokeratin (CK7) [2] and GATA-binding protein 3 (GATA3) [3] are two commonly used markers to confirm breast origin. CK7 was expressed in 97% of triple negative breast cancer with 14.5% demonstrating less than 20% tumor cell staining [11]. Its expression was lost in most sarcomatous (23% positivity) and fibromatosis-like (17% positivity) components, but was still retained in 71% of the matrix-producing component of metaplastic breast cancer [12]
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