ATBF1-a messenger RNA expression is correlated with better prognosis in breast cancer.
OBJECTIVE
The AT motif-binding factor 1 (ATBF1) gene was first identified as a suppressor of the alpha-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.


METHODS
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-alpha-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.
Zhang
Zhenhuan
Z
Department of Breast and Endocrine Surgery, Nagoya City University Medical School, Nagoya, Japan.
Yamashita
Hiroko
H
Toyama
Tatsuya
T
Sugiura
Hiroshi
H
Ando
Yoshiaki
Y
Mita
Keiko
K
Hamaguchi
Maho
M
Kawaguchi
Makoto
M
Miura
Yutaka
Y
Iwase
Hirotaka
H
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020816:Amino Acid Motifs; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D017931:DNA Primers / Q000737:chemistry; D018450:Disease Progression; D018572:Disease-Free Survival; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008875:Middle Aged; D015999:Multivariate Analysis; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012313:RNA / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D000509:alpha-Fetoproteins / Q000378:metabolism
D017931:DNA Primers; D047628:Estrogen Receptor alpha; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D011980:Receptors, Progesterone; D000509:alpha-Fetoproteins; C071660:ZFHX3 protein, human; D012313:RNA