Abstract

GATA transcription factors play a wide role in determination of cell differentiation and control of cell proliferation and movement. GATA binding protein-3 (GATA-3) is a member of the GATA family and it plays decisive roles in the differentiation and maintenance of normal luminal cells and the development of Th2 lymphocyte. Decreased GATA-3 expression is associated with poor prognosis in breast cancer. On the other hand, GATA-3 expression correlates with poor prognosis in peripheral T cell lymphoma. However, the correlation of GATA-3 expression with non-small cell lung carcinoma (NSCLC) remains unclear. The aim of this study is to examine the clinicopathological and prognostic value of GATA-3 expression in surgically resected NSCLC. A total of 842 NSCLC were examined. The male:female ratio was 515:327; the age range was between 38 and 85 years of age and the mean age was 71 years. Pathological stage’s ratio (0:I:II:III) was 37:553:151:101. Adenocarcinoma:Squamous cell carcinoma:Others’ ratio was 602:200:40 in histology. Adjuvant chemotherapy was performed in 188 patients. The follow up duration was from 0.4 months to 168.7 months and the mean duration was 61.9 months. Tissue microarray was constructed and GATA-3 expression was analyzed using immunohistochemistry (clone L50-823, F. Hoffmann-La Roche, Ltd., Basel, Switzerland). The GATA-3 staining percentage in tumor cells were classified as follows: (Negative, 0-9%; Positive, 10%≤). The status of GATA-3 staining was correlated with clinicopathological backgrounds, molecular features and patient outcome. The status of GATA-3 staining was as follows: Negative, 808 (96%); Positive, 34 (4%). GATA-3 expression status was associated with sex, smoking history, pathological stage, histology, pleural invasion, p53 protein expression, MIB-1 labeling index and EGFR mutation. Both overall survival (OS) and recurrent-free survival (RFS) were significantly worse in the patients with positive expression of GATA-3 in comparison with those with negative expression of GATA-3 (5-year OS, 55.7% vs. 74.8%, p=0.006; 5-year RFS, 51.5% vs. 66.8%, p=0.016, respectively). In multivariate analyses adjusting for sex, year, smoking history and pStage, positive expression of GATA-3 was found to be an independent predictive factor of both OS (HR=1.76, 95%CI: 1.02-3.05; p=0.042) and RFS (HR=1.66, 95%CI: 1.01-2.74; p=0.046). GATA-3 expression is correlated with poorer prognosis for both OS and RFS in resected NSCLC. Therefore, the evaluation of GATA-3 expression by immunohistochemistry is a potentially useful prognostic marker for postoperative period.

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