| Title |
A diagnostic marker for superficial urothelial bladder carcinoma: lack of nuclear ATBF1 (ZFHX3) by immunohistochemistry suggests malignant progression
|
|---|---|
| Published in |
BMC Cancer, October 2016
|
| DOI | 10.1186/s12885-016-2845-5 |
| Pubmed ID | |
| Authors |
Makoto Kawaguchi, Noboru Hara, Vladimir Bilim, Hiroshi Koike, Mituko Suzuki, Tae-Sun Kim, Nan Gao, Yu Dong, Sheng Zhang, Yuji Fujinawa, Osamu Yamamoto, Hiromi Ito, Yoshihiko Tomita, Yuchi Naruse, Akira Sakamaki, Yoko Ishii, Koichi Tsuneyama, Masaaki Inoue, Johbu Itoh, Masanori Yasuda, Nobuo Sakata, Cha-Gyun Jung, Satoshi Kanazawa, Hiroyasu Akatsu, Hiroshi Minato, Takayuki Nojima, Kiyofumi Asai, Yutaka Miura |
| Abstract |
Pathological stage and grade have limited ability to predict the outcomes of superficial urothelial bladder carcinoma at initial transurethral resection (TUR). AT-motif binding factor 1 (ATBF1) is a tumor suppressive transcription factor that is normally localized to the nucleus but has been detected in the cytoplasm in several cancers. Here, we examined the diagnostic value of the intracellular localization of ATBF1 as a marker for the identification of high risk urothelial bladder carcinoma. Seven anti-ATBF1 antibodies were generated to cover the entire ATBF1 sequence. Four human influenza hemagglutinin-derived amino acid sequence-tagged expression vectors with truncated ATBF1 cDNA were constructed to map the functional domains of nuclear localization signals (NLSs) with the consensus sequence KR[X10-12]K. A total of 117 samples from initial TUR of human bladder carcinomas were analyzed. None of the patients had received chemotherapy or radiotherapy before pathological evaluation. ATBF1 nuclear localization was regulated synergistically by three NLSs on ATBF1. The cytoplasmic fragments of ATBF1 lacked NLSs. Patients were divided into two groups according to positive nuclear staining of ATBF1, and significant differences in overall survival (P = 0.021) and intravesical recurrence-free survival (P = 0.013) were detected between ATBF1+ (n = 110) and ATBF1- (n = 7) cases. Multivariate analysis revealed that ATBF1 staining was an independent prognostic factor for intravesical recurrence-free survival after adjusting for cellular grading and pathological staging (P = 0.008). Cleavage of ATBF1 leads to the cytoplasmic localization of ATBF1 fragments and downregulates nuclear ATBF1. Alterations in the subcellular localization of ATBF1 due to fragmentation of the protein are related to the malignant character of urothelial carcinoma. Pathological evaluation using anti-ATBF1 antibodies enabled the identification of highly malignant cases that had been overlooked at initial TUR. Nuclear localization of ATBF1 indicates better prognosis of urothelial carcinoma. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 38 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 38 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Master | 5 | 13% |
| Professor | 4 | 11% |
| Professor > Associate Professor | 4 | 11% |
| Student > Bachelor | 4 | 11% |
| Student > Ph. D. Student | 4 | 11% |
| Other | 8 | 21% |
| Unknown | 9 | 24% |
| Readers by discipline | Count | As % |
|---|---|---|
| Medicine and Dentistry | 7 | 18% |
| Agricultural and Biological Sciences | 4 | 11% |
| Nursing and Health Professions | 3 | 8% |
| Biochemistry, Genetics and Molecular Biology | 2 | 5% |
| Psychology | 2 | 5% |
| Other | 7 | 18% |
| Unknown | 13 | 34% |
Attention Score in Context
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#20,447,499
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Outputs of similar age from BMC Cancer
#90
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