Diagnostic utility and sensitivities of GATA3 antibodies in triple-negative breast cancer

Abstract

GATA3 is implicated in mammary epithelial development and breast cancer progression and is an evolving immunohistochemical marker in breast cancer. Often associated with estrogen receptor (ER) signaling, GATA3 expression has been reported in ER-negative breast cancers, but systematic evaluation of GATA3 expression in a large set of triple-negative breast cancers (TNBC) is lacking. Given low sensitivities of mammaglobin (MGB) and GCDFP15 in metastatic TNBC, additional markers for site of origin identification would be useful in this context. We examined immunohistochemical expression of GATA3 in a large group of treatment-naive TNBC (n = 111) and ER-positive (n = 39) and HER2-positive (n = 31) breast cancers with commonly used antibody clones, HG3-31 (GATA3-H) and L50-823 (GATA3-L), and compared GATA3, MGB, and GCDFP15. Respectively, GATA3-L and GATA3-H were positive in 66% and 44% of TNBC (P = .002), 93% and 79% of ER-/HER2+ tumors (P = .596), and 100% of ER+/HER2- and ER+/HER2+ tumors (P = 1.00 each). GATA3-L was technically and diagnostically more sensitive than GATA3-H in TNBC and was technically more sensitive in other subtypes. MGB (26%) and GCDFP15 (16%) were less sensitive for TNBC than other subtypes (P < .001). Notably, 56% and 36% of MGB-/GCDFP15- TNBC were positive with GATA3-L and GATA3-H, respectively (P = .027). Seventy percent of TNBC were positive for GATA3-L, MGB, or GCDFP15 compared with 49% using GATA3-H in the panel. GATA3 is a diagnostically useful marker for TNBC and is more sensitive than MGB and GCDFP15 combined. GATA3-L is more sensitive for TNBC than GATA3-H, and an immunopanel of GATA3-L, MGB, and GCDFP15 provides optimal diagnostic sensitivity for TNBC.

Keywords: GATA3; GCDFP15; Mammaglobin; Metastasis; Triple-negative breast cancer.