4.4 Article

The impact of the effectiveness of GATA3 as a prognostic factor in breast cancer

Journal

HUMAN PATHOLOGY
Volume 80, Issue -, Pages 219-230

Publisher

W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1016/j.humpath.2018.06.004

Keywords

GATA3; Breast cancer; Overall survival; Prognostic factor; Estrogen receptor

Categories

Funding

  1. Health and Welfare surcharge of tobacco products grant [MOHW107-TDU-B-212-114014]
  2. TMU Research Center of Cancer Translational Medicine from The Featured Areas Research Center Program by the Ministry of Education (MOE) in Taiwan
  3. Ministry of Science and Technology, Taiwan [MOST105-2320-B-038-053-MY3, MOST106-2320-B-038-046, MOST106-2314-B-038-053-MY3, MOST 106-2320-B-038-061 -MY3, MOST104-2314-B-038-059-MY3]

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The transcription factor GATA3 plays a significant role in mammary gland development and differentiation. We analyzed expression of GATA3 in breast cancer (BC) cell lines and clinical specimens from BC patients in Taiwan. Semiquantitative reverse-transcription polymerase chain reaction (RT-PCR), quantitative real-time PCR were carried out to determine the mRNA level of GATA3 from 241 pairs of matched tumor and adjacent normal tissues from anonymous female donors. GATA3 immunohistochemistry (IHC) staining and H-score were performed (n = 25). Inducing and silencing of GATA3 were done by exposure MCF-7 cell line to nicotine or curcumin, respectively. GATA3 expression was detected in most of the estrogen receptor-positive (ER+) tumor specimens (176/241, 73%) compared with paired normal tissues (65/241, 27%) (P<.001). The GATA3 level was highest in Luminal A, and independent t-tests revealed higher GATA3 was associated with ER+ (P=.018) and BC stages (stage II, and stage IV). Nuclear protein expression of GATA3 was detected in tumor tissues (P<.001) with higher H-score in Luminal A patients (P=.012). Kaplan-Meier survival analyses showed that ER+/progesterone receptor (PgR)+ and lower grade BC patients with relatively high GATA3 had better clinical overall survival (OS). GATA3 regulates ER alpha and BCL-2 as BC lumina! subtype markers. Cox univariate and multivariate analyses demonstrated that the expression of GATA3 was an effective predictor of the risk of death. We demonstrated a correlation between GATA3 expression and only ER+ and suggest that a higher GATA3 expression is a good prognostic factor for OS for ER+ BC patients. (C) 2018 Elsevier Inc. All rights reserved.

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