Skip to main content
Top
Published in: Breast Cancer 6/2021

01-11-2021 | Breast Cancer | Original Article

TP53 signature diagnostic system using multiplex reverse transcription–polymerase chain reaction system enables prediction of prognosis of breast cancer patients

Authors: Shin Takahashi, Takafumi Fukui, Tadashi Nomizu, Yoichiro Kakugawa, Fumisyoshi Fujishima, Takanori Ishida, Noriaki Ohuchi, Chikashi Ishioka

Published in: Breast Cancer | Issue 6/2021

Login to get access

Abstract

Background

TP53 status based on TP53 signature, a gene expression profile to determine the presence or absence of TP53 mutation, is an independent prognostic factor of breast cancer. The purpose of this study was to develop a simple diagnostic system for TP53 signature status.

Methods

We developed a multiplex reverse transcription–polymerase chain reaction system to determine TP53 status. Based on this system, prospectively collected 189 patients with stage I and II breast cancer were determined to have TP53 mutant signature or TP53 wild-type signature. The prognostic significance of the TP53 signature by the diagnostic system was analyzed.

Results

The diagnostic accuracy of TP53 status and reproducibility of this diagnosis system was confirmed. Using the diagnostic system, 89 patients were classified as TP53 mutant signature and the remaining 100 cases were classified as TP53 wild-type signature. Recurrence-free survival (RFS) among patients with TP53 mutant signature was significantly shorter than that among those with TP53 wild-type signature. On univariate and multivariate analyses, the TP53 signature status was an independent predictor of RFS. RFS among patients with TP53 mutant signature was significantly shorter than that among those with TP53 wild-type signature in a cohort of estrogen receptor-positive breast cancer. Although a difference was not significant, no recurrent cases was observed in TP53 wild-type signature group in triple negative breast cancer.

Conclusion

This simple and precise diagnostic system to determine TP53 signature status may help in prognostic assessment, therapeutic decision-making, and treatment optimization in patients with breast cancer.
Appendix
Available only for authorised users
Literature
1.
go back to reference Reis-Filho JS, Pusztai L. Gene expression profiling in breast cancer: classification, prognostication, and prediction. Lancet. 2011;378(9805):1812–23.CrossRef Reis-Filho JS, Pusztai L. Gene expression profiling in breast cancer: classification, prognostication, and prediction. Lancet. 2011;378(9805):1812–23.CrossRef
2.
go back to reference Sparano JA, Gray RJ, Makower DF, Pritchard KI, Albain KS, Hayes DF, et al. Prospective validation of a 21-gene expression assay in breast cancer. N Engl J Med. 2015;373(21):2005–14.CrossRef Sparano JA, Gray RJ, Makower DF, Pritchard KI, Albain KS, Hayes DF, et al. Prospective validation of a 21-gene expression assay in breast cancer. N Engl J Med. 2015;373(21):2005–14.CrossRef
3.
go back to reference Albain KS, Barlow WE, Shak S, Hortobagyi GN, Livingston RB, Yeh IT, et al. Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial. Lancet Oncol. 2010;11(1):55–65.CrossRef Albain KS, Barlow WE, Shak S, Hortobagyi GN, Livingston RB, Yeh IT, et al. Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial. Lancet Oncol. 2010;11(1):55–65.CrossRef
4.
go back to reference Paik S, Tang G, Shak S, Kim C, Baker J, Kim W, et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol. 2006;24(23):3726–34.CrossRef Paik S, Tang G, Shak S, Kim C, Baker J, Kim W, et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol. 2006;24(23):3726–34.CrossRef
5.
go back to reference Cardoso F, van’t Veer LJ, Bogaerts J, Slaets L, Viale G, Delaloge S, et al. 70-gene signature as an aid to treatment decisions in early-stage breast cancer. N Engl J Med. 2016;375(8):717–29.CrossRef Cardoso F, van’t Veer LJ, Bogaerts J, Slaets L, Viale G, Delaloge S, et al. 70-gene signature as an aid to treatment decisions in early-stage breast cancer. N Engl J Med. 2016;375(8):717–29.CrossRef
6.
go back to reference van de Vijver MJ, He YD, van’t Veer LJ, Dai H, Hart AA, Voskuil DW, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med. 2002;347(25):1999–2009.CrossRef van de Vijver MJ, He YD, van’t Veer LJ, Dai H, Hart AA, Voskuil DW, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med. 2002;347(25):1999–2009.CrossRef
7.
go back to reference Gnant M, Filipits M, Greil R, Stoeger H, Rudas M, Bago-Horvath Z, et al. Predicting distant recurrence in receptor-positive breast cancer patients with limited clinicopathological risk: using the PAM50 Risk of Recurrence score in 1478 postmenopausal patients of the ABCSG-8 trial treated with adjuvant endocrine therapy alone. Ann Oncol. 2014;25(2):339–45.CrossRef Gnant M, Filipits M, Greil R, Stoeger H, Rudas M, Bago-Horvath Z, et al. Predicting distant recurrence in receptor-positive breast cancer patients with limited clinicopathological risk: using the PAM50 Risk of Recurrence score in 1478 postmenopausal patients of the ABCSG-8 trial treated with adjuvant endocrine therapy alone. Ann Oncol. 2014;25(2):339–45.CrossRef
8.
go back to reference Parker JS, Mullins M, Cheang MC, Leung S, Voduc D, Vickery T, et al. Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol. 2009;27(8):1160–7.CrossRef Parker JS, Mullins M, Cheang MC, Leung S, Voduc D, Vickery T, et al. Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol. 2009;27(8):1160–7.CrossRef
9.
go back to reference Soussi T, Beroud C. Assessing TP53 status in human tumours to evaluate clinical outcome. Nat Rev Cancer. 2001;1(3):233–40.CrossRef Soussi T, Beroud C. Assessing TP53 status in human tumours to evaluate clinical outcome. Nat Rev Cancer. 2001;1(3):233–40.CrossRef
10.
go back to reference Olivier M, Langerod A, Carrieri P, Bergh J, Klaar S, Eyfjord J, et al. The clinical value of somatic TP53 gene mutations in 1,794 patients with breast cancer. Clin Cancer Res. 2006;12(4):1157–67.CrossRef Olivier M, Langerod A, Carrieri P, Bergh J, Klaar S, Eyfjord J, et al. The clinical value of somatic TP53 gene mutations in 1,794 patients with breast cancer. Clin Cancer Res. 2006;12(4):1157–67.CrossRef
11.
12.
go back to reference Geisler S, Lonning PE, Aas T, Johnsen H, Fluge O, Haugen DF, et al. Influence of TP53 gene alterations and c-erbB-2 expression on the response to treatment with doxorubicin in locally advanced breast cancer. Cancer Res. 2001;61(6):2505–12.PubMed Geisler S, Lonning PE, Aas T, Johnsen H, Fluge O, Haugen DF, et al. Influence of TP53 gene alterations and c-erbB-2 expression on the response to treatment with doxorubicin in locally advanced breast cancer. Cancer Res. 2001;61(6):2505–12.PubMed
13.
go back to reference Bertheau P, Plassa F, Espie M, Turpin E, de Roquancourt A, Marty M, et al. Effect of mutated TP53 on response of advanced breast cancers to high-dose chemotherapy. Lancet (London, England). 2002;360(9336):852–4.CrossRef Bertheau P, Plassa F, Espie M, Turpin E, de Roquancourt A, Marty M, et al. Effect of mutated TP53 on response of advanced breast cancers to high-dose chemotherapy. Lancet (London, England). 2002;360(9336):852–4.CrossRef
14.
go back to reference Takahashi S, Moriya T, Ishida T, Shibata H, Sasano H, Ohuchi N, et al. Prediction of breast cancer prognosis by gene expression profile of TP53 status. Cancer Sci. 2008;99(2):324–32.CrossRef Takahashi S, Moriya T, Ishida T, Shibata H, Sasano H, Ohuchi N, et al. Prediction of breast cancer prognosis by gene expression profile of TP53 status. Cancer Sci. 2008;99(2):324–32.CrossRef
15.
go back to reference Miller LD, Smeds J, George J, Vega VB, Vergara L, Ploner A, et al. An expression signature for p53 status in human breast cancer predicts mutation status, transcriptional effects, and patient survival. Proc Natl Acad Sci USA. 2005;102(38):13550–5.CrossRef Miller LD, Smeds J, George J, Vega VB, Vergara L, Ploner A, et al. An expression signature for p53 status in human breast cancer predicts mutation status, transcriptional effects, and patient survival. Proc Natl Acad Sci USA. 2005;102(38):13550–5.CrossRef
16.
go back to reference Yamaguchi S, Takahashi S, Mogushi K, Izumi Y, Nozaki Y, Nomizu T, et al. Molecular and clinical features of the TP53 signature gene expression profile in early-stage breast cancer. Oncotarget. 2018;9(18):14193–206.CrossRef Yamaguchi S, Takahashi S, Mogushi K, Izumi Y, Nozaki Y, Nomizu T, et al. Molecular and clinical features of the TP53 signature gene expression profile in early-stage breast cancer. Oncotarget. 2018;9(18):14193–206.CrossRef
17.
go back to reference Uji K, Naoi Y, Kagara N, Shimoda M, Shimomura A, Maruyama N, et al. Significance of TP53 mutations determined by next-generation “deep” sequencing in prognosis of estrogen receptor-positive breast cancer. Cancer Lett. 2014;342(1):19–26.CrossRef Uji K, Naoi Y, Kagara N, Shimoda M, Shimomura A, Maruyama N, et al. Significance of TP53 mutations determined by next-generation “deep” sequencing in prognosis of estrogen receptor-positive breast cancer. Cancer Lett. 2014;342(1):19–26.CrossRef
18.
go back to reference Lehmann BD, Ding Y, Viox DJ, Jiang M, Zheng Y, Liao W, et al. Evaluation of public cancer datasets and signatures identifies TP53 mutant signatures with robust prognostic and predictive value. BMC Cancer. 2015;15:179.CrossRef Lehmann BD, Ding Y, Viox DJ, Jiang M, Zheng Y, Liao W, et al. Evaluation of public cancer datasets and signatures identifies TP53 mutant signatures with robust prognostic and predictive value. BMC Cancer. 2015;15:179.CrossRef
19.
go back to reference Oshima K, Naoi Y, Kishi K, Nakamura Y, Iwamoto T, Shimazu K, et al. Gene expression signature of TP53 but not its mutation status predicts response to sequential paclitaxel and 5-FU/epirubicin/cyclophosphamide in human breast cancer. Cancer Lett. 2011;307(2):149–57.CrossRef Oshima K, Naoi Y, Kishi K, Nakamura Y, Iwamoto T, Shimazu K, et al. Gene expression signature of TP53 but not its mutation status predicts response to sequential paclitaxel and 5-FU/epirubicin/cyclophosphamide in human breast cancer. Cancer Lett. 2011;307(2):149–57.CrossRef
20.
go back to reference Marchetti A, Buttitta F, Pellegrini S, Campani D, Diella F, Cecchetti D, et al. p53 mutations and histological type of invasive breast carcinoma. Cancer Res. 1993;53(19):4665–9.PubMed Marchetti A, Buttitta F, Pellegrini S, Campani D, Diella F, Cecchetti D, et al. p53 mutations and histological type of invasive breast carcinoma. Cancer Res. 1993;53(19):4665–9.PubMed
21.
go back to reference Dobes P, Podhorec J, Coufal O, Jureckova A, Petrakova K, Vojtesek B, et al. Influence of mutation type on prognostic and predictive values of TP53 status in primary breast cancer patients. Oncol Rep. 2014;32(4):1695–702.CrossRef Dobes P, Podhorec J, Coufal O, Jureckova A, Petrakova K, Vojtesek B, et al. Influence of mutation type on prognostic and predictive values of TP53 status in primary breast cancer patients. Oncol Rep. 2014;32(4):1695–702.CrossRef
Metadata
Title
TP53 signature diagnostic system using multiplex reverse transcription–polymerase chain reaction system enables prediction of prognosis of breast cancer patients
Authors
Shin Takahashi
Takafumi Fukui
Tadashi Nomizu
Yoichiro Kakugawa
Fumisyoshi Fujishima
Takanori Ishida
Noriaki Ohuchi
Chikashi Ishioka
Publication date
01-11-2021
Publisher
Springer Singapore
Published in
Breast Cancer / Issue 6/2021
Print ISSN: 1340-6868
Electronic ISSN: 1880-4233
DOI
https://doi.org/10.1007/s12282-021-01250-z

Other articles of this Issue 6/2021

Breast Cancer 6/2021 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine