Skip to main content
Top
Published in: Breast Cancer 3/2016

01-05-2016 | Original Article

Evaluation of aldehyde dehydrogenase 1 and transcription factors in both primary breast cancer and axillary lymph node metastases as a prognostic factor

Authors: Maiko Ito, Tadahiko Shien, Masako Omori, Taeko Mizoo, Takayuki Iwamoto, Tomohiro Nogami, Takayuki Motoki, Naruto Taira, Hiroyoshi Doihara, Shinichiro Miyoshi

Published in: Breast Cancer | Issue 3/2016

Login to get access

Abstract

Background

Aldehyde dehydrogenase 1 (ALDH1) is a marker of breast cancer stem cells, and the expression of ALDH1 may be a prognostic factor of poor clinical outcome. The epithelial–mesenchymal transition may produce cells with stem-cell-like properties promoted by transcription factors. We investigated the expression of ALDH1 and transcription factors in both primary and metastatic lesions, and prognostic value of them in breast cancer patients with axillary lymph node metastasis (ALNM).

Method

Forty-seven breast cancer patients with ALNM who underwent surgery at Okayama University Hospital from 2002 to 2008 were enrolled. We retrospectively evaluated the levels of ALDH1 and transcription factors, such as Snail, Slug and Twist, in both primary and metastatic lesions by immunohistochemistry.

Results

In primary lesions, the positive rate of ALDH1, Snail, Slug and Twist was 19, 49, 40 and 26 %, respectively. In lymph nodes, that of ALDH1, Snail, Slug and Twist was 21, 32, 13 and 23 %, respectively. The expression of ALDH1 or transcription factors alone was not significantly associated with a poor prognosis. However, co-expression of ALDH1 and Slug in primary lesions was associated with a shorter DFS (P = 0.009).

Conclusions

The evaluation of the co-expression of ALDH1 and transcription factors in primary lesions may be useful in prognosis of node-positive breast cancers.
Literature
1.
go back to reference Goldhirsch A, Winer EP, Coates AS, Gelber RD, Piccart-Gebhart M, Thurlimann B, et al. Personalizing the treatment of women with early breast cancer: highlights of the St Gallen international expert consensus on the primary therapy of early breast cancer 2013. Ann Oncol. 2013;24:2206–23.CrossRefPubMedPubMedCentral Goldhirsch A, Winer EP, Coates AS, Gelber RD, Piccart-Gebhart M, Thurlimann B, et al. Personalizing the treatment of women with early breast cancer: highlights of the St Gallen international expert consensus on the primary therapy of early breast cancer 2013. Ann Oncol. 2013;24:2206–23.CrossRefPubMedPubMedCentral
2.
go back to reference Wicha MS, Liu S, Dontu G. Cancer stem cells: an old idea—a paradigm shift. Cancer Res. 2006;66:1883–90 (discussion 1895–1896).CrossRefPubMed Wicha MS, Liu S, Dontu G. Cancer stem cells: an old idea—a paradigm shift. Cancer Res. 2006;66:1883–90 (discussion 1895–1896).CrossRefPubMed
3.
go back to reference Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, et al. ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell. 2007;1:555–67.CrossRefPubMedPubMedCentral Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, et al. ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell. 2007;1:555–67.CrossRefPubMedPubMedCentral
4.
go back to reference Nogami T, Shien T, Tanaka T, Nishiyama K, Mizoo T, Iwamto T, et al. Expression of ALDH1 in axillary lymph node metastases is a prognostic factor of poor clinical outcome in breast cancer patients with 1-3 lymph node metastases. Breast Cancer. 2014;21:58–65.CrossRefPubMed Nogami T, Shien T, Tanaka T, Nishiyama K, Mizoo T, Iwamto T, et al. Expression of ALDH1 in axillary lymph node metastases is a prognostic factor of poor clinical outcome in breast cancer patients with 1-3 lymph node metastases. Breast Cancer. 2014;21:58–65.CrossRefPubMed
5.
go back to reference Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial-mesenchymal transitions in development and disease. Cell. 2009;139:871–90.CrossRefPubMed Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial-mesenchymal transitions in development and disease. Cell. 2009;139:871–90.CrossRefPubMed
7.
go back to reference Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008;133:704–15.CrossRefPubMedPubMedCentral Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, et al. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008;133:704–15.CrossRefPubMedPubMedCentral
8.
go back to reference Lindley LE, Briegel KJ. Molecular characterization of TGFbeta-induced epithelial-mesenchymal transition in normal finite lifespan human mammary epithelial cells. Biochem Biophys Res Commun. 2010;399:659–64.CrossRefPubMed Lindley LE, Briegel KJ. Molecular characterization of TGFbeta-induced epithelial-mesenchymal transition in normal finite lifespan human mammary epithelial cells. Biochem Biophys Res Commun. 2010;399:659–64.CrossRefPubMed
9.
go back to reference Martin TA, Goyal A, Watkins G, Jiang WG. Expression of the transcription factors snail, slug, and twist and their clinical significance in human breast cancer. Ann Surg Oncol. 2005;12:488–96.CrossRefPubMed Martin TA, Goyal A, Watkins G, Jiang WG. Expression of the transcription factors snail, slug, and twist and their clinical significance in human breast cancer. Ann Surg Oncol. 2005;12:488–96.CrossRefPubMed
10.
go back to reference van Nes JG, de Kruijf EM, Putter H, Faratian D, Munro A, Campbell F, et al. Co-expression of SNAIL and TWIST determines prognosis in estrogen receptor-positive early breast cancer patients. Breast Cancer Res Treat. 2012;133:49–59.CrossRefPubMed van Nes JG, de Kruijf EM, Putter H, Faratian D, Munro A, Campbell F, et al. Co-expression of SNAIL and TWIST determines prognosis in estrogen receptor-positive early breast cancer patients. Breast Cancer Res Treat. 2012;133:49–59.CrossRefPubMed
11.
go back to reference Soini Y, Tuhkanen H, Sironen R, Virtanen I, Kataja V, Auvinen P, et al. Transcription factors zeb1, twist and snai1 in breast carcinoma. BMC Cancer. 2011;11:73.CrossRefPubMedPubMedCentral Soini Y, Tuhkanen H, Sironen R, Virtanen I, Kataja V, Auvinen P, et al. Transcription factors zeb1, twist and snai1 in breast carcinoma. BMC Cancer. 2011;11:73.CrossRefPubMedPubMedCentral
12.
go back to reference Carvalho ST, Stiepcich MM, Fregnani JH, Nonogaki S, Rocha R, Soares FA. Evaluation of prognostic factors in stage IIA breast tumors and their correlation with mortality risk. Clinics. 2011;66:607–12.CrossRefPubMedPubMedCentral Carvalho ST, Stiepcich MM, Fregnani JH, Nonogaki S, Rocha R, Soares FA. Evaluation of prognostic factors in stage IIA breast tumors and their correlation with mortality risk. Clinics. 2011;66:607–12.CrossRefPubMedPubMedCentral
13.
go back to reference Karihtala P, Auvinen P, Kauppila S, Haapasaari KM, Jukkola-Vuorinen A, Soini Y. Vimentin, zeb1 and Sip1 are up-regulated in triple-negative and basal-like breast cancers: association with an aggressive tumour phenotype. Breast Cancer Res Treat. 2013;138:81–90.CrossRefPubMed Karihtala P, Auvinen P, Kauppila S, Haapasaari KM, Jukkola-Vuorinen A, Soini Y. Vimentin, zeb1 and Sip1 are up-regulated in triple-negative and basal-like breast cancers: association with an aggressive tumour phenotype. Breast Cancer Res Treat. 2013;138:81–90.CrossRefPubMed
14.
go back to reference Markiewicz A, Ahrends T, Welnicka-Jaskiewicz M, Seroczynska B, Skokowski J, Jaskiewicz J, et al. Expression of epithelial to mesenchymal transition-related markers in lymph node metastases as a surrogate for primary tumor metastatic potential in breast cancer. J Transl Med. 2012;10:226.CrossRefPubMedPubMedCentral Markiewicz A, Ahrends T, Welnicka-Jaskiewicz M, Seroczynska B, Skokowski J, Jaskiewicz J, et al. Expression of epithelial to mesenchymal transition-related markers in lymph node metastases as a surrogate for primary tumor metastatic potential in breast cancer. J Transl Med. 2012;10:226.CrossRefPubMedPubMedCentral
15.
go back to reference Dong Y, Bi LR, Xu N, Yang HM, Zhang HT, Ding Y, et al. The expression of aldehyde dehydrogenase 1 in invasive primary breast tumors and axillary lymph node metastases is associated with poor clinical prognosis. Pathol Res Pract. 2013;209:555–61.CrossRefPubMed Dong Y, Bi LR, Xu N, Yang HM, Zhang HT, Ding Y, et al. The expression of aldehyde dehydrogenase 1 in invasive primary breast tumors and axillary lymph node metastases is associated with poor clinical prognosis. Pathol Res Pract. 2013;209:555–61.CrossRefPubMed
16.
go back to reference Mieog JS, de Kruijf EM, Bastiaannet E, Kuppen PJ, Sajet A, de Craen AJ, et al. Age determines the prognostic role of the cancer stem cell marker aldehyde dehydrogenase-1 in breast cancer. BMC Cancer. 2012;12:42.CrossRefPubMedPubMedCentral Mieog JS, de Kruijf EM, Bastiaannet E, Kuppen PJ, Sajet A, de Craen AJ, et al. Age determines the prognostic role of the cancer stem cell marker aldehyde dehydrogenase-1 in breast cancer. BMC Cancer. 2012;12:42.CrossRefPubMedPubMedCentral
17.
go back to reference Morimoto K, Kim SJ, Tanei T, Shimazu K, Tanji Y, Taguchi T, et al. Stem cell marker aldehyde dehydrogenase 1-positive breast cancers are characterized by negative estrogen receptor, positive human epidermal growth factor receptor type 2, and high Ki67 expression. Cancer Sci. 2009;100:1062–8.CrossRefPubMed Morimoto K, Kim SJ, Tanei T, Shimazu K, Tanji Y, Taguchi T, et al. Stem cell marker aldehyde dehydrogenase 1-positive breast cancers are characterized by negative estrogen receptor, positive human epidermal growth factor receptor type 2, and high Ki67 expression. Cancer Sci. 2009;100:1062–8.CrossRefPubMed
18.
go back to reference Alkatout I, Wiedermann M, Bauer M, Wenners A, Jonat W, Klapper W. Transcription factors associated with epithelial-mesenchymal transition and cancer stem cells in the tumor centre and margin of invasive breast cancer. Exp Mol Pathol. 2013;94:168–73.CrossRefPubMed Alkatout I, Wiedermann M, Bauer M, Wenners A, Jonat W, Klapper W. Transcription factors associated with epithelial-mesenchymal transition and cancer stem cells in the tumor centre and margin of invasive breast cancer. Exp Mol Pathol. 2013;94:168–73.CrossRefPubMed
19.
go back to reference Baum B, Settleman J, Quinlan MP. Transitions between epithelial and mesenchymal states in development and disease. Semin Cell Dev Biol. 2008;19:294–308.CrossRefPubMed Baum B, Settleman J, Quinlan MP. Transitions between epithelial and mesenchymal states in development and disease. Semin Cell Dev Biol. 2008;19:294–308.CrossRefPubMed
21.
go back to reference Come C, Magnino F, Bibeau F, De Santa Barbara P, Becker KF, Theillet C, et al. Snail and slug play distinct roles during breast carcinoma progression. Clin Cancer Res. 2006;12:5395–402.CrossRefPubMed Come C, Magnino F, Bibeau F, De Santa Barbara P, Becker KF, Theillet C, et al. Snail and slug play distinct roles during breast carcinoma progression. Clin Cancer Res. 2006;12:5395–402.CrossRefPubMed
22.
go back to reference Li J, Zhou BP. Activation of beta-catenin and Akt pathways by Twist are critical for the maintenance of EMT associated cancer stem cell-like characters. BMC Cancer. 2011;11:49.CrossRefPubMedPubMedCentral Li J, Zhou BP. Activation of beta-catenin and Akt pathways by Twist are critical for the maintenance of EMT associated cancer stem cell-like characters. BMC Cancer. 2011;11:49.CrossRefPubMedPubMedCentral
24.
go back to reference Wei L, Liu TT, Wang HH, Hong HM, Yu AL, Feng HP, et al. Hsp27 participates in the maintenance of breast cancer stem cells through regulation of epithelial–mesenchymal transition and nuclear factor-kappaB. Breast Cancer Res. 2011;13:R101.CrossRefPubMedPubMedCentral Wei L, Liu TT, Wang HH, Hong HM, Yu AL, Feng HP, et al. Hsp27 participates in the maintenance of breast cancer stem cells through regulation of epithelial–mesenchymal transition and nuclear factor-kappaB. Breast Cancer Res. 2011;13:R101.CrossRefPubMedPubMedCentral
25.
go back to reference Mallini P, Lennard T, Kirby J, Meeson A. Epithelial-to-mesenchymal transition: what is the impact on breast cancer stem cells and drug resistance. Cancer Treat Rev. 2014;40:341–8.CrossRefPubMed Mallini P, Lennard T, Kirby J, Meeson A. Epithelial-to-mesenchymal transition: what is the impact on breast cancer stem cells and drug resistance. Cancer Treat Rev. 2014;40:341–8.CrossRefPubMed
Metadata
Title
Evaluation of aldehyde dehydrogenase 1 and transcription factors in both primary breast cancer and axillary lymph node metastases as a prognostic factor
Authors
Maiko Ito
Tadahiko Shien
Masako Omori
Taeko Mizoo
Takayuki Iwamoto
Tomohiro Nogami
Takayuki Motoki
Naruto Taira
Hiroyoshi Doihara
Shinichiro Miyoshi
Publication date
01-05-2016
Publisher
Springer Japan
Published in
Breast Cancer / Issue 3/2016
Print ISSN: 1340-6868
Electronic ISSN: 1880-4233
DOI
https://doi.org/10.1007/s12282-015-0583-1

Other articles of this Issue 3/2016

Breast Cancer 3/2016 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