GATA3 as an Adjunct Prognostic Factor in Breast Cancer Patients with Less Aggressive Disease: A Study with a Review of the Literature.

Patrizia Querzoli,Rosa Rinaldi,Elisabetta Kuhn,Massimo Pedriali,Paola Secchiero,Paolo Giorgi Rossi

doi:10.3390/diagnostics11040604

Abstract

Background: GATA binding protein 3 (GATA3) expression is positively correlated with estrogen receptor (ER) expression, but its prognostic value as an independent factor remains unclear. Thus, we undertook the current study to evaluate the expression of GATA3 and its prognostic value in a large series of breast carcinomas (BCs) with long-term follow-up. Methods: A total of 702 consecutive primary invasive BCs resected between 1989 and 1993 in our institution were arranged in tissue microarrays, immunostained for ER, progesterone receptor (PR), ki-67, HER2, p53, and GATA3, and scored. Clinico-pathological data were retrospectively collected. Results: GATA3 was evaluable in 608 (87%) of the 702 cases; it was positive in 413 (68%) cases and negative in 195 (32%) cases. GATA3 positivity was significantly associated with lower grade (p < 0.0001), size (p = 0.0463), stage (p = 0.0049), ER+ (p < 0.0001), PR+ (p < 0.0001), HER2− (p = 0.0175), and p53 wild-type pattern (p < 0.0001). The median follow-up was 183 months, GATA3 positivity was associated with better overall survival (HR 0.70, p = 0.001), and its prognostic value was retained in a multivariate analysis. The association with better overall survival was stronger in patients with grade 1–2, pT1–2, pN0, stage I–II, ER+, PR+, ki-67 < 20%, HER2−, a wild-type p53 immunohistochemical pattern, and in luminal B BC. Conclusions: Our findings indicate that GATA3 is a positive prognostic marker in BC patients, especially in patients with biologically less aggressive BC. Incorporating GATA3 immunohistochemistry into routine practice could help further stratify BC patients for their risk.

Highlights

Medical oncologists treating breast cancer (BC) patients rely on well-known prognostic and predictive factors in order to provide the most appropriate and individualized clinical management
GATA binding protein 3 (GATA3) expression in human BCs is positively associated with estrogen receptor (ER) expression, and is required for cell cycle progression of ER-positive cell lines and coregulated with ER
We found that GATA3 expression was associated with a 20% reduction in the risk of death during a 28-year follow-up time

Summary

Introduction

Medical oncologists treating breast cancer (BC) patients rely on well-known prognostic and predictive factors in order to provide the most appropriate and individualized clinical management. It has been found that, in ER-negative cell lines, GATA3 interacts with wild-type BRCA1, but it is incapable of binding to mutant BRCA1 [9]. This finding is important, since the disruption of the BRCA1/GATA3 interaction could be the biochemical mechanism underlining the aggressive behavior of basal-like BC [9]. GATA binding protein 3 (GATA3) expression is positively correlated with estrogen receptor (ER) expression, but its prognostic value as an independent factor remains unclear. GATA3 positivity was significantly associated with lower grade (p < 0.0001), size (p = 0.0463), stage (p = 0.0049), ER+ (p < 0.0001), PR+ (p < 0.0001), HER2− (p = 0.0175), and p53 wild-type pattern (p < 0.0001). Incorporating GATA3 immunohistochemistry into routine practice could help further stratify BC patients for their risk

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