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

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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.

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References

  1. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Wicha MS, Liu S, Dontu G. Cancer stem cells: an old idea—a paradigm shift. Cancer Res. 2006;66:1883–90 (discussion 1895–1896).

    Article  CAS  PubMed  Google Scholar 

  3. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. 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.

    Article  PubMed  Google Scholar 

  5. Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial-mesenchymal transitions in development and disease. Cell. 2009;139:871–90.

    Article  CAS  PubMed  Google Scholar 

  6. Tomaskovic-Crook E, Thompson EW, Thiery JP. Epithelial to mesenchymal transition and breast cancer. Breast Cancer Res. 2009;11:213.

    Article  PubMed  PubMed Central  Google Scholar 

  7. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. 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.

    Article  CAS  PubMed  Google Scholar 

  9. 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.

    Article  PubMed  Google Scholar 

  10. 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.

    Article  CAS  PubMed  Google Scholar 

  11. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  13. 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.

    Article  CAS  PubMed  Google Scholar 

  14. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. 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.

    Article  CAS  PubMed  Google Scholar 

  16. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. 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.

    Article  CAS  PubMed  Google Scholar 

  18. 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.

    Article  CAS  PubMed  Google Scholar 

  19. Baum B, Settleman J, Quinlan MP. Transitions between epithelial and mesenchymal states in development and disease. Semin Cell Dev Biol. 2008;19:294–308.

    Article  CAS  PubMed  Google Scholar 

  20. Tsuji T, Ibaragi S, Hu GF. Epithelial-mesenchymal transition and cell cooperativity in metastasis. Cancer Res. 2009;69:7135–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. 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.

    Article  CAS  PubMed  Google Scholar 

  22. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Lim S, Becker A, Zimmer A, Lu J, Buettner R, Kirfel J. SNAI1-mediated epithelial-mesenchymal transition confers chemoresistance and cellular plasticity by regulating genes involved in cell death and stem cell maintenance. PLoS One. 2013;8:e66558. doi:10.1371/journal.pone.0066558.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. 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.

    Article  CAS  PubMed  Google Scholar 

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Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of General Thoracic Surgery and Breast and Endocrine Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Kita-ku, Shikata-cho, Okayama, 700-8558, Japan

    Maiko Ito, Tadahiko Shien, Taeko Mizoo, Tomohiro Nogami, Naruto Taira, Hiroyoshi Doihara & Shinichiro Miyoshi

  2. Department of Pathology, Okayama University Hospital, 2-5-1 Kita-ku, Shikata-cho, Okayama, 700-8558, Japan

    Masako Omori

  3. Department of Breast and Endocrine Surgery, Okayama University Hospital, 2-5-1 Kita-ku, Shikata-cho, Okayama, 700-8558, Japan

    Takayuki Iwamoto & Takayuki Motoki

Authors
  1. Maiko Ito
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  2. Tadahiko Shien
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  3. Masako Omori
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  4. Taeko Mizoo
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  5. Takayuki Iwamoto
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  6. Tomohiro Nogami
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  7. Takayuki Motoki
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  8. Naruto Taira
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  9. Hiroyoshi Doihara
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  10. Shinichiro Miyoshi
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Corresponding author

Correspondence to Maiko Ito.

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Ito, M., Shien, T., Omori, M. et al. Evaluation of aldehyde dehydrogenase 1 and transcription factors in both primary breast cancer and axillary lymph node metastases as a prognostic factor. Breast Cancer 23, 437–444 (2016). https://doi.org/10.1007/s12282-015-0583-1

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  • DOI: https://doi.org/10.1007/s12282-015-0583-1

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