Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Diagnostic Pathology
Published in: Diagnostic Pathology 1/2011

Open Access 01-12-2011 | Research

Differential expression of HIF-1α in CD44+CD24-/low breast ductal carcinomas

Authors: João Paulo Oliveira-Costa, Juliana S Zanetti, Giórgia G Silveira, Danilo F Soave, Lucinei R Oliveira, Verônica A Zorgetto, Fernando A Soares, Sérgio Zucoloto, Alfredo Ribeiro-Silva

Published in: Diagnostic Pathology | Issue 1/2011

Login to get access

Abstract

Background

Cancer stem cell (CSC) hypothesis postulates that tumors are maintained by a self-renewing CSC population that is also capable of differentiating into non-self-renewing cell populations that constitute the bulk of tumor. Stem cells renewal and differentiation can be directly influenced by the oxygen levels of determined tissues, probably by the reduction of oxidative DNA damage in hypoxic regions, thus leading to a friendlier microenvironment, regarding to clonal expansion and for resistance to chemotherapeutic regimens. Furthermore, there have been strong data indicating a pivotal role of hypoxic niche in cancer stem cells development. There are evidence that hypoxia could drive the maintenance of CSC, via HIF-1α expression, but it still to be determined whether hypoxia markers are expressed in breast tumors presenting CD44+CD24-/low immunophenotype.

Methods

Immunohistochemical analysis of CD44+CD24-/low expression and its relationship with hypoxia markers and clinical outcome were evaluated in 253 samples of breast ductal carcinomas. Double-immunolabeling was performed using EnVision Doublestain System (Dako, Carpinteria, CA, USA). Slides were then scanned into high-resolution images using Aperio ScanScope XT and then, visualized in the software Image Scope (Aperio, Vista, CA, USA).

Results

In univariate analysis, CD44+CD24-/low expression showed association with death due to breast cancer (p = 0.035). Breast tumors expressing CD44+CD24-/low immunophenotype showed relationship with HIF-1α (p = 0.039) and negativity for HER-2 (p = 0.013).

Conclusion

Considering that there are strong evidences that the fraction of a tumour considered to be cancer stem cells is plastic depending upon microenvironmental signals, our findings provide further evidence that hypoxia might be related to the worse prognosis found in CD44+CD24-/low positive breast tumors.
Appendix
Available only for authorised users
Literature
1.
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: 3983-8. 10.1073/pnas.0530291100.PubMedCentralCrossRefPubMed
3.
4.
Heddleston JM, Li Z, McLendon RE, Hjelmeland AB, Rich JN: The hypoxic microenvironment maintains glioblastoma stem cells and promotes reprogramming towards a cancer stem cell phenotype. Cell Cycle. 2009, 8: 3274-84. 10.4161/cc.8.20.9701.PubMedCentralCrossRefPubMed
5.
Bar EE, Lin A, Mahairaki V, Matsui W, Eberhart CG: Hypoxia increases the expression of stem-cell markers and promotes clonogenicity in glioblastoma neurospheres. Am J Pathol. 2010, 177: 1491-502. 10.2353/ajpath.2010.091021.PubMedCentralCrossRefPubMed
6.
Hill RP, Marie-Egyptienne DT, Hedley DW: Cancer stem cells, hypoxia and metastasis. Semin Radiat Oncol. 2009, 19: 106-11. 10.1016/j.semradonc.2008.12.002.CrossRefPubMed
7.
Mabjeesh NJ, Amir S: Hypoxia-inducible factor (HIF) in human tumorigenesis. Histol Histopathol. 2007, 22: 559-72.PubMed
8.
Chia SK, Wykoff CC, Watson PH, Han C, Leek RD, Pastorek J, Gatter KC, Ratcliffe P, Harris AL: Prognostic significance of a novel hypoxia-regulated marker, carbonic anhydrase IX, in invasive breast carcinoma. J Clin Oncol. 2001, 19: 3660-8.PubMed
9.
Swinson DE, Jones JL, Richardson D, Wykoff C, Turley H, Pastorek J, Taub N, Harris AL, O'Byrne KJ: Carbonic anhydrase IX expression, a novel surrogate marker of tumor hypoxia, is associated with a poor prognosis in non-small-cell lung cancer. J Clin Oncol. 2003, 21: 473-82. 10.1200/JCO.2003.11.132.CrossRefPubMed
10.
Hussain SA, Ganesan R, Reynolds G, Gross L, Stevens A, Pastorek J: Hypoxia-regulated carbonic anhydrase IX expression is associated with poor survival in patients with invasive breast cancer. Br J Cancer. 2007, 96: 104-9. 10.1038/sj.bjc.6603530.PubMedCentralCrossRefPubMed
11.
Fitzgibbons PL, Page DL, Weaver D, Thor AD, Allred DC, Clark GM, Ruby SG, O'Malley F, Simpson JF, Connolly JL, Hayes DF, Edge SB, Lichter A, Schnitt SJ: Prognostic factors in breast cancer. College of American Pathologists Consensus Statement 1999. Arch Pathol Lab Med. 2000, 124: 966-78.PubMed
12.
Giatromanolaki A, Sivridis E, Fiska A, Koukourakis MI: The CD44+/CD24- phenotype relates to 'triple-negative' state and unfavorable prognosis in breast cancer patients. Med Oncol. 2010,
13.
Chen CL, Chu JS, Su WC, Huang SC, Lee WY: Hypoxia and metabolic phenotypes during breast carcinogenesis: expression of HIF-1alpha, GLUT1, and CAIX. Virchows Arch. 2010, 457: 53-61. 10.1007/s00428-010-0938-0.CrossRefPubMed
14.
Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, Dowsett M, Fitzgibbons PL, Hanna WM, Langer A, McShane LM, Paik S, Pegram MD, Perez EA, Press MF, Rhodes A, Sturgeon C, Taube SE, Tubbs R, Vance GH, van de Vijver M, Wheeler TM, Hayes DF: American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. Arch Pathol Lab Med. 2007, 131: 18-43.PubMed
15.
Liu YH, Xu FP, Rao JY, Zhuang HG, Luo XL, Li L, Luo DL, Zhang F, Xu J: Justification of the change from 10% to 30% for the immunohistochemical HER2 Scoring criterion in breast cancer. Am J Clin Pathol. 2009, 132: 74-9. 10.1309/AJCPG3LCVKPNFJ6R.CrossRefPubMed
16.
Honeth G, Bendahl PO, 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 Res. 2008, 10: R53-10.1186/bcr2108.PubMedCentralCrossRefPubMed
17.
Morel A-P, Lièvre M, Thomas C, Hinkal G, Ansieau S, Puisieux A: Generation of breast cancer stem cells through epithelial-mesenchymal transition. PLoS ONE. 2008, 3: e2888-10.1371/journal.pone.0002888.PubMedCentralCrossRefPubMed
18.
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
19.
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: 1096-102. 10.1016/j.humpath.2007.12.003.CrossRefPubMed
20.
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: 1154-9.PubMed
21.
Balic M, Lin H, Young L, Hawes D, Giuliano A, McNamara G, Datar RH, Cote RJ: Most early disseminated cancer cells detected in bone marrow of breast cancer patients have a putative breast cancer stem cell phenotype. Clin Cancer Res. 2006, 12: 5615-21. 10.1158/1078-0432.CCR-06-0169.CrossRefPubMed
22.
Oliveira LR, Jeffrey SS, Ribeiro-Silva A: Stem cells in human breast cancer. Histol Histopathol. 2010, 25: 371-85.PubMed
23.
Oliveras-Ferraros C, Vazquez-Martin A, Martin-Castillo B, Cufí S, Del Barco S, Lopez-Bonet E, Brunet J, Menendez JA: Dynamic emergence of the mesenchymal CD44(pos)CD24(neg/low) phenotype in HER2-gene amplified breast cancer cells with de novo resistance to trastuzumab (Herceptin). Biochem Biophys Res Commun. 2010, 397: 27-33. 10.1016/j.bbrc.2010.05.041.CrossRefPubMed
24.
Heddleston JM, Li Z, Lathia JD, Bao S, Hjelmeland AB, Rich JN: Hypoxia inducible factors in cancer stem cells. Br J Cancer. 2010, 102: 789-95. 10.1038/sj.bjc.6605551.PubMedCentralCrossRefPubMed
25.
Soeda A, Park M, Lee D, Mintz A, Androutsellis-Theotokis A, McKay RD, Engh J, Iwama T, Kunisada T, Kassam AB, Pollack IF, Park DM: Hypoxia promotes expansion of the CD133-positive glioma stem cells through activation of HIF-1alpha. Oncogene. 2009, 28: 3949-59. 10.1038/onc.2009.252.CrossRefPubMed
26.
Påhlman S, Stockhausen MT, Fredlund E, Axelson H: Notch signaling in neuroblastoma. Semin Cancer Biol. 2004, 14: 365-73. 10.1016/j.semcancer.2004.04.016.CrossRefPubMed
27.
Jögi A, Øra I, Nilsson H, Lindeheim A, Makino Y, Poellinger L, Axelson H, Påhlman S: Hypoxia alters gene expression in human neuroblastoma cells toward an immature and neural crest-like phenotype. Proc Natl Acad Sci USA. 2002, 99: 7021-6. 10.1073/pnas.102660199.PubMedCentralCrossRefPubMed
28.
McCord AM, Jamal M, Shankavaram UT, Lang FF, Camphausen K, Tofilon PJ: Physiologic oxygen concentration enhances the stem-like properties of CD133+ human glioblastoma cells in vitro. Mol Cancer Res. 2009, 7: 489-97. 10.1158/1541-7786.MCR-08-0360.CrossRefPubMed
29.
Ezashi T, Das P, Roberts RM: Low O2 tensions and the prevention of differentiation of hES cells. Proc Natl Acad Sci USA. 2005, 102: 4783-8. 10.1073/pnas.0501283102.PubMedCentralCrossRefPubMed
30.
Kakarala M, Wicha MS: Implications of the cancer stem-cell hypothesis for breast cancer prevention and therapy. J Clin Oncol. 2008, 26: 2813-2820. 10.1200/JCO.2008.16.3931.PubMedCentralCrossRefPubMed
Metadata
Title
Differential expression of HIF-1α in CD44+CD24-/low breast ductal carcinomas
Authors
João Paulo Oliveira-Costa
Juliana S Zanetti
Giórgia G Silveira
Danilo F Soave
Lucinei R Oliveira
Verônica A Zorgetto
Fernando A Soares
Sérgio Zucoloto
Alfredo Ribeiro-Silva
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Diagnostic Pathology / Issue 1/2011
Electronic ISSN: 1746-1596
DOI
https://doi.org/10.1186/1746-1596-6-73

Other articles of this Issue 1/2011

Diagnostic Pathology 1/2011 Go to the issue

Review

Review of juxtaglomerular cell tumor with focus on pathobiological aspect

Research

Expression of MK-1 and RegIV and its clinicopathological significances in the benign and malignant lesions of gallbladder

Research

Immunohistochemical profiles of claudin-3 in primary and metastatic prostatic adenocarcinoma

Methodology

An inexpensive method of small paraffin tissue microarrays using mechanical pencil tips

Case Report

Primary angiosarcoma of the ovary with prominent fibrosis of the ovarian stroma. Case report of an 81-year old patient

Research

Subtype distribution of lymphomas in Southwest China: Analysis of 6,382 cases using WHO classification in a single institution