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ALDH1 is a better clinical indicator for relapse of invasive ductal breast cancer than the CD44+/CD24 phenotype

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Abstract

Breast cancer stem cells are thought to be associated with metastasis and poor prognosis, but their clinical importance remains poorly understood. The aim of this study was to investigate whether certain phenotypes of breast cancer stem cells were clinically important factors regarding metastasis. Patients with primary breast cancer (n = 121) were included in this study. Breast cancer stem cells were identified by immunohistochemical staining of CD44, CD24, and aldehyde dehydrogenase 1 (ALDH1) in tumor tissues from primary and recurrent or metastatic lesions. CD44+/CD24 cells and ALDH1+ cells were considered breast cancer stem cells. Sixty-five patients had metastatic or recurrent tumors. ALDH1+ tumors were significantly associated with a high rate of metastasis or recurrence (63.1 %; P = 0.026). Although there was no significant association between the proportion of CD44+/CD24 tumor cells and metastasis rates, a high proportion of CD44+/CD24 tumor cells was a risk factor for metastasis or recurrence (P = 0.035). Changes in the proportion of CD44+/CD24 or ALDH1+ tumor cells between primary lesions and recurrent lesions were studied in 27 patients. The proportion of ALDH1+ tumor cells increased significantly (P = 0.019) after recurrence, but the proportion of CD44+/CD24 tumor cells did not. Our findings suggest that ALDH1+ and CD44+/CD24 breast cancer stem cells play significant roles in metastasis. The rate of ALDH1+ cells appears to be a better predictive marker of breast cancer metastasis than the CD44+/CD24 phenotype.

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References

  1. Lapidot T, Sirard C, Vormoor J, Murdoch B, Hoang T, Caceres-Cortes J, et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature. 1994;367(6464):645–8.

    Article  CAS  PubMed  Google Scholar 

  2. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA. 2003;100(7):3983–8.

    Article  CAS  PubMed  Google Scholar 

  3. Kim CF, Jackson EL, Woolfenden AE, Lawrence S, Babar I, Vogel S, et al. Identification of bronchioalveolar stem cells in normal lung and lung cancer. Cell. 2005;121(6):823–35.

    Article  CAS  PubMed  Google Scholar 

  4. O’Brien CA, Pollett A, Gallinger S, Dick JE. A human colon cancer cell capable of initiating tumour growth in immunodeficient mice. Nature. 2007;445(7123):106–10.

    Article  PubMed  Google Scholar 

  5. Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, et al. Identification of human brain tumour initiating cells. Nature. 2004;432(7015):396–401.

    Article  CAS  PubMed  Google Scholar 

  6. Abraham BK, Fritz P, McClellan M, Hauptvogel P, Athelogou M, Brauch H. Prevalence of CD44+/CD24−/low cells in breast cancer may not be associated with clinical outcome but may favor distant metastasis. Clin Cancer Res. 2005;11(3):1154–9.

    CAS  PubMed  Google Scholar 

  7. Liu R, Wang X, Chen GY, Dalerba P, Gurney A, Hoey T, et al. The prognostic role of a gene signature from tumorigenic breast-cancer cells. N Engl J Med. 2007;356(3):217–26.

    Article  CAS  PubMed  Google Scholar 

  8. Grantzdorffer I, Yumlu S, Gioeva Z, von Wasielewski R, Ebert MP, Rocken C. Comparison of different tissue sampling methods for protein extraction from formalin-fixed and paraffin-embedded tissue specimens. Exp Mol Pathol. 2010;88(1):190–6.

    Article  PubMed  Google Scholar 

  9. Sprung RW Jr, Brock JW, Tanksley JP, Li M, Washington MK, Slebos RJ, et al. Equivalence of protein inventories obtained from formalin-fixed paraffin-embedded and frozen tissue in multidimensional liquid chromatography–tandem mass spectrometry shotgun proteomic analysis. Mol Cell Proteomics. 2009;8(8):1988–98.

    Article  CAS  PubMed  Google Scholar 

  10. Dowsett M, Allred C, Knox J, Quinn E, Salter J, Wale C, et al. Relationship between quantitative estrogen and progesterone receptor expression and human epidermal growth factor receptor 2 (HER-2) status with recurrence in the Arimidex, Tamoxifen, Alone or in Combination trial. J Clin Oncol. 2008;26(7):1059–65.

    Article  CAS  PubMed  Google Scholar 

  11. Mylona E, Giannopoulou I, Fasomytakis E, Nomikos A, Magkou C, Bakarakos P, et al. The clinicopathologic and prognostic significance of CD44+/CD24(−/low) and CD44−/CD24+ tumor cells in invasive breast carcinomas. Hum Pathol. 2008;39(7):1096–102.

    Article  CAS  PubMed  Google Scholar 

  12. Croker AK, Goodale D, Chu J, Postenka C, Hedley BD, Hess DA, et al. High aldehyde dehydrogenase and expression of cancer stem cell markers selects for breast cancer cells with enhanced malignant and metastatic ability. J Cell Mol Med. 2009;13(8B):2236–52.

    Article  PubMed  Google Scholar 

  13. 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(5):555–67.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Resetkova E, Reis-Filho JS, Jain RK, Mehta R, Thorat MA, Nakshatri H, et al. Prognostic impact of ALDH1 in breast cancer: a story of stem cells and tumor microenvironment. Breast Cancer Res Treat. 2010;123(1):97–108.

    Article  PubMed  Google Scholar 

  15. Sheridan C, Kishimoto H, Fuchs RK, Mehrotra S, Bhat-Nakshatri P, Turner CH, et al. CD44+/CD24− breast cancer cells exhibit enhanced invasive properties: an early step necessary for metastasis. Breast Cancer Res. 2006;8(5):R59.

    Article  PubMed Central  PubMed  Google Scholar 

  16. Sun S, Wang Z. ALDH high adenoid cystic carcinoma cells display cancer stem cell properties and are responsible for mediating metastasis. Biochem Biophys Res Commun. 2010;396(4):843–8.

    Article  CAS  PubMed  Google Scholar 

  17. Wakamatsu Y, Sakamoto N, Oo HZ, Naito Y, Uraoka N, Anami K, et al. Expression of cancer stem cell markers ALDH1, CD44 and CD133 in primary tumor and lymph node metastasis of gastric cancer. Pathol Int. 2012;62(2):112–9.

    Article  PubMed  Google Scholar 

  18. Wang Y, Zhe H, Gao P, Zhang N, Li G, Qin J. Cancer stem cell marker ALDH1 expression is associated with lymph node metastasis and poor survival in esophageal squamous cell carcinoma: a study from high incidence area of northern China. Dis Esophagus. 2012;25(6):560–5.

    Article  CAS  PubMed  Google Scholar 

  19. Voduc KD, Cheang MC, Tyldesley S, Gelmon K, Nielsen TO, Kennecke H. Breast cancer subtypes and the risk of local and regional relapse. J Clin Oncol. 2010;28(10):1684–91.

    Article  PubMed  Google Scholar 

  20. Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res. 2007;13(15 Pt 1):4429–34.

    Article  PubMed  Google Scholar 

  21. Lin NU, Vanderplas A, Hughes ME, Theriault RL, Edge SB, Wong YN, et al. Clinicopathologic features, patterns of recurrence, and survival among women with triple-negative breast cancer in the National Comprehensive Cancer Network. Cancer. 2012;118(22):5463–72.

    Article  PubMed Central  PubMed  Google Scholar 

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All authors declare no conflict.

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Correspondence to Qiang Sun.

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Ying Zhong and Songjie Shen have contributed equally to this study.

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Zhong, Y., Shen, S., Zhou, Y. et al. ALDH1 is a better clinical indicator for relapse of invasive ductal breast cancer than the CD44+/CD24 phenotype. Med Oncol 31, 864 (2014). https://doi.org/10.1007/s12032-014-0864-0

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  • DOI: https://doi.org/10.1007/s12032-014-0864-0

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