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Published in: Journal of Experimental & Clinical Cancer Research 1/2012

Open Access 01-12-2012 | Research

CD44+/CD24- phenotype contributes to malignant relapse following surgical resection and chemotherapy in patients with invasive ductal carcinoma

Authors: Yan Lin, Ying Zhong, Heng Guan, Xiaohui Zhang, Qiang Sun

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2012

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Abstract

Background

Invasive ductal carcinoma is the most common type of breast malignancy, with varying molecular features and resistance to treatment. Although CD44+/CD24- cells are believed to act as breast cancer stem cells and to be linked to poor prognosis in some patients, the association between these cells and tumor recurrence or metastasis in all or some types of invasive ductal carcinoma is unclear.

Methods

A total of 147 randomly selected primary and secondary invasive ductal carcinoma samples were assayed for expression of CD44, CD24, ER, PR, and Her2. The association between the proportions of CD44+/CD24- tumor cells and the clinico-pathological features of these patients was evaluated.

Results

CD44+/CD24- tumor cells were detected in 70.1% of the tumors, with a median proportion of 5.8%. The proportion of CD44+/CD24- tumor cells was significantly associated with lymph node involvement (P = 0.026) and PR status (P = 0.038), and was correlated with strong PR status in patients with recurrent or metastatic tumors (P = 0.046) and with basal-like features (p = 0.05). The median disease-free survival (DFS) of patients with and without CD44+/CD24-/low tumor cells were 22.9 ± 2.2 months and 35.9 ± 3.8 months, and the median overall survival (OS) of patients with and without CD44+/CD24-/low tumor cells were 39.3 ± 2.6 months and 54.0 ± 3.5 months, respectively, and with both univariate and multivariate analyses showing that the proportion of CD44+/CD24-/low tumor cells was strongly correlated with DFS and OS.

Conclusion

The prevalence of CD44+/CD24- tumor cells varied greatly in invasive ductal carcinomas, with the occurrence of this phenotype high in primary tumors with high PR status and in secondary tumors. Moreover, this phenotype was significantly associated with shorter cumulative DFS and OS. Thus, the CD44+/CD24- phenotype may be an important factor for malignant relapse following surgical resection and chemotherapy in patients with invasive ductal carcinoma.
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Literature
1.
go back to reference Jemal A, Siegel R, Xu J, Ward E: Cancer statistics, 2010. CA Cancer J Clin. 2010, 60: 277-300. 10.3322/caac.20073.CrossRefPubMed Jemal A, Siegel R, Xu J, Ward E: Cancer statistics, 2010. CA Cancer J Clin. 2010, 60: 277-300. 10.3322/caac.20073.CrossRefPubMed
2.
go back to reference Ozbay T, Nahta R: Delphinidin inhibits HER2 and Erk1/2 signaling and suppresses growth of HER2-overexpressing and triple negative breast cancer cell lines. Breast Cancer: Basic and Clinical Research. 2011, 5: 143-154. Ozbay T, Nahta R: Delphinidin inhibits HER2 and Erk1/2 signaling and suppresses growth of HER2-overexpressing and triple negative breast cancer cell lines. Breast Cancer: Basic and Clinical Research. 2011, 5: 143-154.
3.
go back to reference 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: 1684-1691. 10.1200/JCO.2009.24.9284.CrossRefPubMed 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: 1684-1691. 10.1200/JCO.2009.24.9284.CrossRefPubMed
4.
go back to reference Reya T, Morrison SJ, Clarke MF, Weissman IL: Stem cells, cancer, and cancer stem cells. Nature. 2001, 414: 105-111. 10.1038/35102167.CrossRefPubMed Reya T, Morrison SJ, Clarke MF, Weissman IL: Stem cells, cancer, and cancer stem cells. Nature. 2001, 414: 105-111. 10.1038/35102167.CrossRefPubMed
5.
go back to reference Nakshatri H, Srour EF, Badve S: Breast cancer stem cells and intrinsic subtypes: controversies rage on. Current Stem Cell Research & Therapy. 2009, 4: 50-60. 10.2174/157488809787169110.CrossRef Nakshatri H, Srour EF, Badve S: Breast cancer stem cells and intrinsic subtypes: controversies rage on. Current Stem Cell Research & Therapy. 2009, 4: 50-60. 10.2174/157488809787169110.CrossRef
6.
go back to reference Shipitsin M, Campbell LL, Argani P, Weremowicz S, Bloushtain-Qimron N, Yao J, Nikolskaya T, Serebryiskaya T, Beroukhim R, Hu M, Halushka MK, Sukumar S, Parker LM, Anderson KS, Harris LN, Garber JE, Richardson AL, Schnitt SJ, Nikolsky Y, Gelman RS, Polyak K: Molecular definition of breast tumor heterogeneity. Cancer Cell. 2007, 11: 259-273. 10.1016/j.ccr.2007.01.013.CrossRefPubMed Shipitsin M, Campbell LL, Argani P, Weremowicz S, Bloushtain-Qimron N, Yao J, Nikolskaya T, Serebryiskaya T, Beroukhim R, Hu M, Halushka MK, Sukumar S, Parker LM, Anderson KS, Harris LN, Garber JE, Richardson AL, Schnitt SJ, Nikolsky Y, Gelman RS, Polyak K: Molecular definition of breast tumor heterogeneity. Cancer Cell. 2007, 11: 259-273. 10.1016/j.ccr.2007.01.013.CrossRefPubMed
7.
go back to reference Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, Campbell LL, Polyak K, Brisken C, Yang J, Weinberg RA: The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008, 133: 704-715. 10.1016/j.cell.2008.03.027.PubMedCentralCrossRefPubMed Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, Campbell LL, Polyak K, Brisken C, Yang J, Weinberg RA: The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell. 2008, 133: 704-715. 10.1016/j.cell.2008.03.027.PubMedCentralCrossRefPubMed
8.
go back to reference Visvader JE, Lindeman GJ: Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer. 2008, 8: 755-768. 10.1038/nrc2499.CrossRefPubMed Visvader JE, Lindeman GJ: Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer. 2008, 8: 755-768. 10.1038/nrc2499.CrossRefPubMed
9.
go back to reference Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, Rijn M, Jeffrey SS, Thorsen T, Quist H, Matese JC, Brown PO, Botstein D, Lønning PE, Børresen-Dale A: Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA. 2001, 98: 10869-10874. 10.1073/pnas.191367098.PubMedCentralCrossRefPubMed Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, Rijn M, Jeffrey SS, Thorsen T, Quist H, Matese JC, Brown PO, Botstein D, Lønning PE, Børresen-Dale A: Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA. 2001, 98: 10869-10874. 10.1073/pnas.191367098.PubMedCentralCrossRefPubMed
10.
go back to reference Sheridan C, Kishimoto H, Fuchs RK, Mehrotra S, Bhat-Nakshatri P, Turner CH, Goulet R, Badve S, Nakshatri H: CD44+/CD24- breast cancer cells exhibit enhanced invasive properties: an early step necessary for metastasis. Breast Cancer Res. 2006, 8: R59-10.1186/bcr1610.PubMedCentralCrossRefPubMed Sheridan C, Kishimoto H, Fuchs RK, Mehrotra S, Bhat-Nakshatri P, Turner CH, Goulet R, Badve S, Nakshatri H: CD44+/CD24- breast cancer cells exhibit enhanced invasive properties: an early step necessary for metastasis. Breast Cancer Res. 2006, 8: R59-10.1186/bcr1610.PubMedCentralCrossRefPubMed
11.
go back to reference 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: 3983-3988. 10.1073/pnas.0530291100.PubMedCentralCrossRefPubMed 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: 3983-3988. 10.1073/pnas.0530291100.PubMedCentralCrossRefPubMed
12.
go back to reference Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, Jacquemier J, Viens P, Kleer C, Liu S, Schott A, Hayes D, Birnbaum D, Wicha MS, Dontu G: ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell. 2007, 1: 555-567. 10.1016/j.stem.2007.08.014.PubMedCentralCrossRefPubMed Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, Jacquemier J, Viens P, Kleer C, Liu S, Schott A, Hayes D, Birnbaum D, Wicha MS, Dontu G: ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell. 2007, 1: 555-567. 10.1016/j.stem.2007.08.014.PubMedCentralCrossRefPubMed
13.
go back to reference Raouf A, Zhao Y, To K, Stingl J, Delaney A, Barbara M, Iscove N, Jones S, McKinney S, Emerman J, Aparicio S, Marra M, Eaves C: Transcriptome analysis of the normal human mammary cell commitment and differentiation process. Cell Stem Cell. 2008, 3: 109-118. 10.1016/j.stem.2008.05.018.CrossRefPubMed Raouf A, Zhao Y, To K, Stingl J, Delaney A, Barbara M, Iscove N, Jones S, McKinney S, Emerman J, Aparicio S, Marra M, Eaves C: Transcriptome analysis of the normal human mammary cell commitment and differentiation process. Cell Stem Cell. 2008, 3: 109-118. 10.1016/j.stem.2008.05.018.CrossRefPubMed
14.
go back to reference Mylona E, Giannopoulou I, Fasomytakis E, Nomikos A, Magkou C, Bakarakos P, Nakopoulou L: The clinicopathologic and prognostic significance of CD44+/CD24(−/low) and CD44-/CD24+ tumor cells in invasive breast carcinomas. Hum Pathol. 2008, 39 (7): 1096-1102. 10.1016/j.humpath.2007.12.003.CrossRefPubMed Mylona E, Giannopoulou I, Fasomytakis E, Nomikos A, Magkou C, Bakarakos P, Nakopoulou L: The clinicopathologic and prognostic significance of CD44+/CD24(−/low) and CD44-/CD24+ tumor cells in invasive breast carcinomas. Hum Pathol. 2008, 39 (7): 1096-1102. 10.1016/j.humpath.2007.12.003.CrossRefPubMed
15.
go back to reference UICC: International Union Against Cancer (UICC), TNM Classification of Malignant Tumours. 2002, Wiley-Liss, New York, 6 edn UICC: International Union Against Cancer (UICC), TNM Classification of Malignant Tumours. 2002, Wiley-Liss, New York, 6 edn
16.
go back to reference Devilee P, Tavassoli FA: World Health Organization: Tumours of the Breast and Female Genital Organs. 2003, Oxford University Press, Oxford [Oxfordshire] Devilee P, Tavassoli FA: World Health Organization: Tumours of the Breast and Female Genital Organs. 2003, Oxford University Press, Oxford [Oxfordshire]
17.
go back to reference Ponti D, Costa A, Zaffaroni N, Pratesi G, Petrangolini G, Coradini D, Pilotti S, Pierotti MA, Daidone MG: Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer Res. 2005, 65: 5506-5511. 10.1158/0008-5472.CAN-05-0626.CrossRefPubMed Ponti D, Costa A, Zaffaroni N, Pratesi G, Petrangolini G, Coradini D, Pilotti S, Pierotti MA, Daidone MG: Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer Res. 2005, 65: 5506-5511. 10.1158/0008-5472.CAN-05-0626.CrossRefPubMed
18.
go back to reference Yeung TM, Gandhi SC, Wilding JL, Muschel R, Bodmer WF: Cancer stem cells from colorectal cancer-derived cell lines. Proc Natl Acad Sci. 2010, 107: 3722-3727. 10.1073/pnas.0915135107.PubMedCentralCrossRefPubMed Yeung TM, Gandhi SC, Wilding JL, Muschel R, Bodmer WF: Cancer stem cells from colorectal cancer-derived cell lines. Proc Natl Acad Sci. 2010, 107: 3722-3727. 10.1073/pnas.0915135107.PubMedCentralCrossRefPubMed
19.
go back to reference 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): 1154-1159.PubMed 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): 1154-1159.PubMed
20.
go back to reference Honeth G, Bendahl P, Ringnér M, Saal LH, Gruvberger-Saal SK, Lövgren K, Grabau D, Fernö M, Borg A, Hegardt C: The CD44+/CD24- phenotype is enriched in basal-like breast tumors. Breast Cancer Research. 2008, 10: R53-10.1186/bcr2108.PubMedCentralCrossRefPubMed Honeth G, Bendahl P, Ringnér M, Saal LH, Gruvberger-Saal SK, Lövgren K, Grabau D, Fernö M, Borg A, Hegardt C: The CD44+/CD24- phenotype is enriched in basal-like breast tumors. Breast Cancer Research. 2008, 10: R53-10.1186/bcr2108.PubMedCentralCrossRefPubMed
21.
22.
go back to reference Liu R, Wang X, Chen GY, Dalerba P, Gurney A, Hoey T, Sherlock G, Lewicki J, Shedden K, Clarke MF: The prognostic role of a gene signature from tumorigenic breast-cancer cells. N Engl J Med. 2007, 356: 217-226. 10.1056/NEJMoa063994.CrossRefPubMed Liu R, Wang X, Chen GY, Dalerba P, Gurney A, Hoey T, Sherlock G, Lewicki J, Shedden K, Clarke MF: The prognostic role of a gene signature from tumorigenic breast-cancer cells. N Engl J Med. 2007, 356: 217-226. 10.1056/NEJMoa063994.CrossRefPubMed
23.
go back to reference Zhou L, Jiang Y, Yan T, Di G, Shen Z, Shao Z, Lu J: The prognostic role of cancer stem cells in breast cancer: a meta-analysis of published literatures. Breast cancer research and treatment. 2010, 122: 795-801. 10.1007/s10549-010-0999-4.CrossRefPubMed Zhou L, Jiang Y, Yan T, Di G, Shen Z, Shao Z, Lu J: The prognostic role of cancer stem cells in breast cancer: a meta-analysis of published literatures. Breast cancer research and treatment. 2010, 122: 795-801. 10.1007/s10549-010-0999-4.CrossRefPubMed
24.
25.
go back to reference Lopez JL, Camenisch TD, Stevens MV, Sands BJ, McDonald J, Schroeder JA: CD44 attenuates metastatic invasion during breast cancer progression. Cancer Res. 2005, 65: 6755-6763. 10.1158/0008-5472.CAN-05-0863.CrossRefPubMed Lopez JL, Camenisch TD, Stevens MV, Sands BJ, McDonald J, Schroeder JA: CD44 attenuates metastatic invasion during breast cancer progression. Cancer Res. 2005, 65: 6755-6763. 10.1158/0008-5472.CAN-05-0863.CrossRefPubMed
26.
go back to reference Fillmore CM, Kuperwasser C: Human breast cancer cell lines contain stem-like cells that self-renew, give rise to phenotypically diverse progeny and survive chemotherapy. Breast Cancer Res. 2008, 10: R25-10.1186/bcr1982.PubMedCentralCrossRefPubMed Fillmore CM, Kuperwasser C: Human breast cancer cell lines contain stem-like cells that self-renew, give rise to phenotypically diverse progeny and survive chemotherapy. Breast Cancer Res. 2008, 10: R25-10.1186/bcr1982.PubMedCentralCrossRefPubMed
27.
go back to reference Louie E, Nik S, Chen J, Schmidt M, Song B, Pacson C, Chen XF, Park S, Ju J, Chen EI: Identification of a stem-like cell population by exposing metastatic breast cancer cell lines to repetitive cycles of hypoxia and reoxygenation. Breast Cancer Research. 2010, 12: R94-10.1186/bcr2773.PubMedCentralCrossRefPubMed Louie E, Nik S, Chen J, Schmidt M, Song B, Pacson C, Chen XF, Park S, Ju J, Chen EI: Identification of a stem-like cell population by exposing metastatic breast cancer cell lines to repetitive cycles of hypoxia and reoxygenation. Breast Cancer Research. 2010, 12: R94-10.1186/bcr2773.PubMedCentralCrossRefPubMed
Metadata
Title
CD44+/CD24- phenotype contributes to malignant relapse following surgical resection and chemotherapy in patients with invasive ductal carcinoma
Authors
Yan Lin
Ying Zhong
Heng Guan
Xiaohui Zhang
Qiang Sun
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2012
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/1756-9966-31-59

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