GATA3 expression and its relationship with clinicopathological parameters in invasive breast carcinomas.

ABSTRACT

GATA3, as a transcription factor, is associated with estrogen receptor (ER) expression and necessary for luminal cell differentiation in mammary glands. Association of GATA3 expression with clinicopathological parameters, molecular subtypes of tumors, disease free survival (DFS) and overall survival (OS) for breast carcinoma patients were evaluated in this study. We immunohistochemically stained GATA3, CK5/6, EGFR, CK14 and vimentin on tissue microarray blocks of 457 invasive breast carcinomas. Tumors are sub-classified as luminal A, luminal B, HER2 expressing, basal-like and null type according to their hormonal status with cerbB2, CK 5/6 and EGFR expressions. Follow-up data for 254 cases were obtained. 215/457 (47%) tumors were GATA3 positive. GATA3 expression was inversely correlated with mitotic count (p<0.0001), nuclear grade (p=0.001), histological grade (p=0.001), tumor necrosis (p=0.001), stromal lymphocytic response (p<0.01), nipple invasion (p=0.01), metastasis (p=0.03), vimentin (p=0.0003), EGFR (p=0.015) and CK14 (p=0.001) expressions; and directly associated with ER (p<0.0001) and progesterone receptor (PR) (p<0.0001) expressions. Luminal A carcinomas had the highest frequency for GATA-3 (140/245), however basal-like carcinomas had the lowest (1/42) (p<0.0001). None of the medullary and metaplastic carcinomas expressed GATA3. GATA3 was associated with good DFS and OS (p=0.001 and p=0.0009) and was an independent prognostic factor for OS. GATA3 expression, regardless of the subtype, may have a prognostic significance for breast carcinomas through its ability to promote the differentiation of luminal progenitor cells.