GATA3 expression in advanced breast cancer: prognostic value and organ-specific relapse.
OBJECTIVE
GATA3 is a transcription factor regulating luminal cell differentiation in the mammary glands and has been implicated in the luminal types of breast carcinoma. The prognostic significance of GATA3 in breast cancer remains controversial.


METHODS
In this study, we assessed the prognostic value of the molecule in a subset of 62 advanced breast cancers and 10 control breast cancers (no metastasis after follow-up).


RESULTS
GATA3 expression levels in luminal tumors of advanced stage were significantly higher than that of the human epidermal growth factor receptor 2 (HER2) subtype and triple-negative carcinomas, as expected, but were similar to those of the luminal controls. Furthermore, 88% of nonluminal tumors showed variable GATA3 expression, for which the HER2 subtype had significantly higher GATA3 expression than that of the triple-negative carcinomas. Interestingly, GATA3 levels were significantly lower in carcinomas with lung relapse compared to those with metastatic recurrence to other organs, thus reflecting the findings in animal models. No significant difference was observed between tumors with bone relapse and those metastasized to nonskeletal sites. Moreover, high GATA3 expression was significantly associated with favorable relapse-free survival and overall survival.


CONCLUSIONS
These findings suggest that GATA3 may not act solely as a luminal differentiation marker, and further uncovering the molecular pathways by which GATA3 regulates the downstream targets will be crucial to our understanding of breast cancer dissemination.
From the Department of Pathology, School of Medicine and.
Brandi C
BC
McCleskey
From the Department of Pathology, School of Medicine and.
Thuy L
TL
Penedo
Department of Biostatistics, School of Public Health, University of Alabama at Birmingham.
Kui
K
Zhang
From the Department of Pathology, School of Medicine and.
Omar
O
Hameed
From the Department of Pathology, School of Medicine and.
Gene P
GP
Siegal
From the Department of Pathology, School of Medicine and swei@uab.edu.
Shi
S
Wei
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001940:Breast / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; D050990:GATA3 Transcription Factor; D018719:Erb-b2 Receptor Tyrosine Kinases; C494749:GATA3 protein, human; C508053:ERBB2 protein, human
Breast cancer; GATA3; Metastasis; Prognosis; Subtype