630 Prospective cloning of functionally distinct breast cancer cells by use of markers from a normal human breast lineage hierarchy

Abstract

GATA-binding protein 3 (GATA3) is a diagnostically useful immunohistochemical marker of breast cancer. Because of its strong association with estrogen receptor expression, GATA3 has markedly reduced sensitivity in triple-negative breast cancer (TNBC). We constructed a tissue microarray using a large series of TNBCs and evaluated GATA3 expression by TNBC subtype as defined by surrogate immunohistochemical markers. A total of 205 TNBCs were classified into cancers of the molecular apocrine type (n = 23, 11.2%), claudin-low type (n = 21, 10.2%), basal-like type (n = 91, 44.4%), mixed type (n = 62, 30.2%), and null type (n = 8, 3.9%). The GATA3 scores (staining intensity × proportion) were categorized as negative (0), focally positive (1-10), or positive (11-300). GATA3 staining was negative in 153 cancers (74.6%), focally positive in 11 (5.4%), and positive in 41 (20.0%). The rate of focal positivity or positivity for GATA3 was significantly higher in the molecular apocrine type (73.9%, 17/23) than in other types of TNBCs (P = .001). The mean GATA3 score of molecular apocrine–type TNBC was significantly higher than that of the other types (P = .001) and differed significantly between androgen receptor (AR)–positive and AR-negative TNBCs (P < .001). In conclusion, GATA3 expression was correlated strongly with AR-positive, molecular apocrine–type TNBCs. Co-expression of AR and GATA3 is a specific feature of molecular apocrine–type TNBC, which may serve as a diagnostic aid for cancer of unknown primary.