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High Expression of Stem Cell Marker ALDH1 is Associated with Reduced BRCA1 in Invasive Breast Carcinomas

  • Madjd, Zahra (Department of Pathology, Tehran University of Medical Sciences) ;
  • Ramezani, Babak (Department of Pathology, Tehran University of Medical Sciences) ;
  • Molanae, Saadat (Department of Pathology, Milad Hospital) ;
  • Asadi-Lari, Mohsen (Oncopathology Research Centre, Tehran University of Medical Sciences)
  • Published : 2012.06.30

Abstract

Background: Cancer stem cells (CSC) have been described in a variety of malignancies, including breast carcinomas. Among several markers, aldehyde dehydrogenase 1 (ALDH1) has been identified as reliable for breast cancer stem cells. Knockdown of BRCA1 in primary breast epithelial cells leads to an increase in cells expressing ALDH1. Methods: We examined 127 breast carcinomas for expression of ALDH1, using immunohistochemistry and correlated with clinicopathological parameters as well as the BRAC1 status. Results: Comparing the results for both ALDH1 and BRCA1 expression showed a significant inverse association between the two, indicating that reduced BRCA1 was more often seen in breast cancer cells expressing ALDH1 (p-value = 0.044). A total of 24/110 (22%) of tumours displayed the ALDH1 + / BRCA1 -/low phenotype, which showed a trend for a relation with a high grade (p-value= 0.056). Cytoplasmic expression of ALDH1 was not correlated with tumour characteristics. Conclusion: Taken together, our findings suggest that increased ALDH1 is inversely correlated with decreased BRCA1 in a series of unselected breast carcinomas. Therefore, ALDH1 positive (cancer stem) cells with reduced BRCA1 phenotype may indicate a subset of patients for whom specific targeting of the CSC marker ALDH1 and more aggressive adjuvant treatment is appropriate.

Keywords

Breast cancer;cancer stem cells;ALDH1

References

  1. Abraham BK, Fritz P, McClellan M, et al (2005). Prevalence of CD44+/CD24-/low cells in breast cancer may not be associated with clinical outcome but may favor distant metastasis. Clin Cancer Res, 11, 1154-9.
  2. Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (2003). Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA, 100, 3983-8. https://doi.org/10.1073/pnas.0530291100
  3. Balicki D (2007). Moving forward in human mammary stem cell biology and breast cancer prognostication using ALDH1. Cell Stem Cell, 1, 485-7. https://doi.org/10.1016/j.stem.2007.10.015
  4. Collins AT, Berry PA, Hyde C, Stower MJ, Maitland NJ (2005). Prospective identification of tumorigenic prostate cancer stem cells. Cancer Res, 65, 10946-51. https://doi.org/10.1158/0008-5472.CAN-05-2018
  5. Costa FF, Le Blanc K, Brodin B (2007). Cancer/testis antigens, stem cells and cancer. Stem Cells, 25, 707-11.
  6. Diehn M, Clarke MF (2006). Cancer stem cells and radiotherapy: new insights into tumor radioresistance. J Natl Cancer Inst, 98, 1755-7. https://doi.org/10.1093/jnci/djj505
  7. Ellis IO, Galea M, Broughton N, et al (1992). Pathological prognostic factors in breast cancer. II. Histological type. Relationship with survival in a large study with long-term follow-up. Histopathology, 20, 479-89.
  8. Elston CW, Ellis IO (1991). Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term followup. Histopathology, 19, 403-10. https://doi.org/10.1111/j.1365-2559.1991.tb00229.x
  9. Eyler CE, Rich JN (2008). Survival of the fittest: cancer stem cells in therapeutic resistance and angiogenesis. J Clin Oncol, 26, 2839-45. https://doi.org/10.1200/JCO.2007.15.1829
  10. Fang D, Nguyen TK, Leishear K, et al (2005). A tumorigenic subpopulation with stem cell properties in melanomas. Cancer Res, 65, 9328-37. https://doi.org/10.1158/0008-5472.CAN-05-1343
  11. Ginestier C, Hur MH, Charafe-Jauffret E, et al (2007). ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell, 1, 555-67. https://doi.org/10.1016/j.stem.2007.08.014
  12. Ginestier C, Wicha MS (2007). Mammary stem cell number as a determinate of breast cancer risk. Breast Cancer Res, 9, 109. https://doi.org/10.1186/bcr1741
  13. Glinsky GV, Berezovska O, Glinskii AB (2005). Microarray analysis identifies a death-from-cancer signature predicting therapy failure in patients with multiple types of cancer. J Clin Invest, 115, 1503-21. https://doi.org/10.1172/JCI23412
  14. Heerma van Voss MR, Van der Groep P, Bart J, Van der Wall E, Van Diest PJ (2011). Expression of the stem cell marker ALDH1 in BRCA1 related breast cancer. Cell Oncol, 34, 3-10. https://doi.org/10.1007/s13402-010-0007-3
  15. Jiang F, Qiu Q, Khanna A, et al (2009). Aldehyde dehydrogenase 1 is a tumor stem cell-associated marker in lung cancer. Mol Cancer Res, 7, 330-8. https://doi.org/10.1158/1541-7786.MCR-08-0393
  16. Kunju LP, Cookingham C, Toy KA, et al (2011). EZH2 and ALDH-1 mark breast epithelium at risk for breast cancer development. Mod Pathol, 24, 786-93. https://doi.org/10.1038/modpathol.2011.8
  17. Li C, Heidt DG, Dalerba P, et al (2007). Identification of pancreatic cancer stem cells. Cancer Res, 67, 1030-7. https://doi.org/10.1158/0008-5472.CAN-06-2030
  18. Li X, Lewis MT, Huang J, et al (2008). Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy. J Natl Cancer Inst, 100, 672-9. https://doi.org/10.1093/jnci/djn123
  19. Liu S, Ginestier C, Charafe-Jauffret E, et al (2008). BRCA1 regulates human mammary stem/progenitor cell fate. Proc Natl Acad Sci USA, 105, 1680-5. https://doi.org/10.1073/pnas.0711613105
  20. Madjd Z, Mehrjerdi AZ, Sharifi AM, et al (2009). CD44+ cancer cells express higher levels of the anti-apoptotic protein Bcl-2 in breast tumours. Cancer Immun, 9, 4.
  21. Madjd Z, Karimi A, Molanae S, Asadi-Lari M (2011). BRCA1 protein expression level and CD44+ phenotype in breast cancer patients. Cell Journal, 13, 155-62.
  22. Matsui W, Huff CA, Wang Q, et al (2004). Characterization of clonogenic multiple myeloma cells. Blood, 103, 2332-6. https://doi.org/10.1182/blood-2003-09-3064
  23. McCarty KS Jr, Miller LS, Cox EB, Konrath J, McCarty KS Sr (1985). Estrogen receptor analyses. Correlation of biochemical and immunohistochemical methods using monoclonal antireceptor antibodies. Arch Pathol Lab Med, 109, 716-21.
  24. Morimoto K, Kim SJ, Tanei T, et al (2009). 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, 100, 1062-8. https://doi.org/10.1111/j.1349-7006.2009.01151.x
  25. Nalwoga H, Arnes JB, Wabinga H, Akslen LA (2010). Expression of aldehyde dehydrogenase 1 (ALDH1) is associated with basal-like markers and features of aggressive tumours in African breast cancer. Br J Cancer, 102, 369-75. https://doi.org/10.1038/sj.bjc.6605488
  26. Neumeister V, Agarwal S, Bordeaux J, Camp RL, Rimm DL (2010). In situ identification of putative cancer stem cells by multiplexing ALDH1, CD44, and cytokeratin identifies breast cancer patients with poor prognosis. Am J Pathol, 176, 2131-8. https://doi.org/10.2353/ajpath.2010.090712
  27. Neumeister V, Rimm D (2010). Is ALDH1 a good method for definition of breast cancer stem cells? Breast Cancer Res Treat, 123, 109-11. https://doi.org/10.1007/s10549-009-0656-y
  28. Phillips TM, McBride WH, Pajonk F (2006). The response of CD24(-/low)/CD44+ breast cancer-initiating cells to radiation. J Natl Cancer Inst, 98, 1777-85. https://doi.org/10.1093/jnci/djj495
  29. Pinder SE, Ellis IO, Galea M, et al (1994). Pathological prognostic factors in breast cancer. III. Vascular invasion: relationship with recurrence and survival in a large study with long-term follow-up. Histopathology, 24, 41-7. https://doi.org/10.1111/j.1365-2559.1994.tb01269.x
  30. Resetkova E, Reis-Filho JS, Jain RK, et al (2010). Prognostic impact of ALDH1 in breast cancer: a story of stem cells and tumor microenvironment. Breast Cancer Res Treat, 123, 97-108. https://doi.org/10.1007/s10549-009-0619-3
  31. Trimboli AJ, Cantemir-Stone CZ, Li F, et al (2009). Pten in stromal fibroblasts suppresses mammary epithelial tumours. Nature, 461, 1084-91. https://doi.org/10.1038/nature08486
  32. Vasiliou V, Pappa A, Petersen DR (2000). Role of aldehyde dehydrogenases in endogenous and xenobiotic metabolism. Chem Biol Interact, 129, 1-19. https://doi.org/10.1016/S0009-2797(00)00211-8
  33. Visvader JE, Lindeman GJ (2008). Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer, 8, 755-68. https://doi.org/10.1038/nrc2499
  34. Yoshioka T, Umekita Y, Ohi Y, et al (2011). Aldehyde dehydrogenase 1 expression is a predictor of poor prognosis in node-positive breast cancers: a long-term follow-up study. Histopathology, 58, 608-16. https://doi.org/10.1111/j.1365-2559.2011.03781.x
  35. Zhou L, Jiang Y, Yan T, et al (2010). The prognostic role of cancer stem cells in breast cancer: a meta-analysis of published literatures. Breast Cancer Res Treat, 122, 795-801. https://doi.org/10.1007/s10549-010-0999-4

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