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Poster display session

2633 - Development of TP53 signature diagnostic system using multiplex RT-PCR and observational study to confirm the prognostic value of TP53 signature in breast cancer

Date

11 Sep 2017

Session

Poster display session

Presenters

Shin Takahashi

Citation

Annals of Oncology (2017) 28 (suppl_5): v573-v594. 10.1093/annonc/mdx390

Authors

S. Takahashi1, T. Fukui2, T. Nomizu3, Y. Kakugawa4, T. Ishida5, S. Yamaguchi6, S. Kato6, N. Ohuchi5, N. Gondo2, C. Ishioka7

Author affiliations

  • 1 Department Of Medical Oncology, Tohoku University Hospital, 980-8575 - Sendai/JP
  • 2 Biomedical Business Department, FALCO Biosystems, 613-0036 - Kyoto/JP
  • 3 Department Of Surgery, Hoshi General Hospital, Koriyama/JP
  • 4 Department Of Breast Oncology, Miyagi Cancer Center Hospital, Natori/JP
  • 5 Department Of Surgical Oncology, Tohoku University Graduate School of Medicine, Sendai/JP
  • 6 Department Of Clinical Oncology, Juntendo University Graduated School, Tokyo/JP
  • 7 Department Of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai/JP
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Resources

Abstract 2633

Background

The structural mutation status of TP53 gene is well known independent prognostic factor of breast cancer. We have reported that status of the TP53 mutation is predictable by expression profile of 33 genes (‘TP53 signature’) in breast cancer. The TP53 signature was reported to be one of the best predictors of prognosis and therapeutic effect by meta-analysis (BMC Cancer, 2015). The aim of this study is to develop a simple diagnostic system for TP53 signature using multiplex RT–PCR and confirm the prognostic value of TP53 signature.

Methods

We made the multiplex RT-PCR system consists of 26 genes, 23 genes from theTP53 predictive genes and 3 internal control genes. TP53 signature status was determined by the ratio of the sum of expression levels of 16 genes that were upregulated in tumors with TP53 mutation to the sum of expression values of 7 genes downregulated in tumors withTP53 mutation. Cutoff value was set at 1.11 to maximize the sensitivity to detect the TP53 mutant signature. Using a 217 breast cancer case cohort, which was prospectively collected from 2007 to 2010, the relationship between the TP53 signature status and clinicopathological features and TP53 structural mutations were analyzed. And we validated the prognostic value of TP53 signature in 191 stage I-II patients.

Results

Of 217 patients, 102 patients were assigned to the TP53 mutant signature. TP53 structural mutation was observed in 35.1% of patients with TP53 mutant signature and 6.3% of patients with TP53 wild-type signature. In 191 stage I-II patients, RFS of the patients withTP53 mutant signature showed significantly shorter than the patients with wild-type signature. Similar result was observed in 164 ER positive patients. In both univariate and multivariate analyses, TP53 signature status showed independent and better correlation to RFS than tumor size, LN status, stage, ER status and TP53 structural mutation status in stage I-II patients.

Conclusions

We developed the diagnostic system to determine TP53 signature status using multiplex RT-PCR. The TP53 status diagnosed by this system could be one of the prognostic biomarker of breast cancer.

Clinical trial identification

UMIN000005172.

Legal entity responsible for the study

Ethics Committee at the Tohoku University Hospital.

Funding

The Grants-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.

Disclosure

All authors have declared no conflicts of interest.

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