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ATBF1-A Messenger RNA Expression Is Correlated with Better Prognosis in Breast Cancer

Departments of ¹ Breast and Endocrine Surgery and ² Bioregulation Research, Nagoya City University Medical School, Nagoya, Japan and ³ Department of Pathology, Niigata Rosai Hospital, Japan Labor Health and Welfare Organization, Niigata, Japan

Requests for reprints: Hirotaka Iwase, Department of Breast and Endocrine Surgery, Nagoya City University Hospital, Kawasumi 1, Mizuho-ku, Nagoya 467-8601, Japan. Phone: 52-853-8231; Fax: 52-853-6440; E-mail: h.iwase{at}med.nagoya-cu.ac.jp.

Purpose: The AT motif-binding factor 1 (ATBF1) gene was first identified as a suppressor of the -fetoprotein (AFP) gene through its binding to an AT-rich enhancer element of this gene. The gene is located at chromosome 16q22.3-q23.1 where loss of heterozygosity has been observed in various malignant tumors, especially in breast cancer. It was also found that in highly malignant AFP-producing gastric cancer cells the expression of AFP is inhibited by ATBF1-A. This led us to hypothesize that there was a link between levels of ATBF1 expression and the metastatic potential of breast cancer and also, therefore, the prognosis of these patients.

Experimental Design: In the present study, the level of ATBF1-A mRNA expression was analyzed using quantitative real-time reverse transcriptase-PCR, in 153 female patients with invasive carcinoma of the breast. ATBF1-A protein expression was also determined by immunohistochemistry from available 90 cases of paired tissues. An association was sought between ATBF1-A expression and various clinicopathologic factors.

Results: ATBF1-A mRNA was expressed at significantly higher levels in breast cancer patients with no axillary lymph node involvement, with small tumors measuring <2 cm and in estrogen receptor-–positive tumors. By contrast, no relationship was found between ATBF1-A mRNA expression and ATBF1-A protein expression, and also no relationship was found between ATBF1-A protein expression and any of the other clinicopathologic factors. Patients expressing high levels of ATBF1-A mRNA tended to have a better prognosis than those expressing low levels. Univariate and multivariate prognostic analyses showed that ATBF1-A mRNA expression is an independent prognostic factor for disease-free survival.

Conclusions: In breast cancer, levels of ATBF1-A mRNA may serve as a predictive indicator of lymph node metastasis. The results of this study also imply that ATBF1-A gene expression may have potential both as a marker of endocrine responsiveness and also as a prognostic indicator for breast cancer progression.

Key Words: Estrogen receptor • Progesterone receptor • Real-time RT-PCR

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