Relationship of CD44+CD24-/low breast cancer stem cells and axillary lymph node metastasis

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Abstract

Background

Axillary node staging plays an important role in the prognostic evaluation and planning of adjuvant treatment. Breast cancer stem cells, identified on the basis of CD44 ⁺CD24 ^-/low expression, are associated with metastases and drug resistance. It is therefore important to investigate the proportion of CD44 ⁺CD24 ^-/low breast cancer stem cells for the diagnosis of metastases in axillary nodes.

Methods

Thirty-two ipsilateral axillary lymph nodes were collected from patients diagnosed with invasive breast cancer. Each lymph node (LN) was divided into two equals – one was examined by H&E staining, while the other was made into a single cell suspension to study the content of CD44 ⁺CD24 ^-/low cells by flow cytometry (FCM). The relationship was investigated between the content of CD44 ⁺CD24 ^-/low cells and metastases in axillary nodes which were confirmed by histology. Associations were tested using the chi-square test (linear-by-linear association), and the significance level was set at a value of p < 0.05.

Results

In the 32 axillary nodes, the level of CD44 ⁺CD24 ^-/low cells was determined to be between 0 and 18.4%: there was no presence of CD44+CD24-/low cells in 9 LNs, of which 2 had confirmed metastasis; there were less than 10% CD44+CD24-/low cells in 12 LNs, of which 6 had confirmed metastasis; and there were more than 10% CD44+CD24-/low cells in 11 LNs, of which 9 had confirmed metastasis. A higher percentage of detected CD44 ⁺CD24 ^-/low cells was significantly associated with more confirmed LN metastases (p = 0.009).

Conclusions

CD44 ⁺CD24 ^-/low breast cancer stem cells might help clinicians to determine the presence of LN metastases. However, its prognostic value remains unclear, while histological diagnosis is still the gold standard.

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Most cited references 17

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Twenty-five-year follow-up of a randomized trial comparing radical mastectomy, total mastectomy, and total mastectomy followed by irradiation.

Bernard Fisher, Jong-Hyeon Jeong, Stewart Anderson … (2002)

In women with breast cancer, the role of radical mastectomy, as compared with less extensive surgery, has been a matter of debate. We report 25-year findings of a randomized trial initiated in 1971 to determine whether less extensive surgery with or without radiation therapy was as effective as the Halsted radical mastectomy. A total of 1079 women with clinically negative axillary nodes underwent radical mastectomy, total mastectomy without axillary dissection but with postoperative irradiation, or total mastectomy plus axillary dissection only if their nodes became positive. A total of 586 women with clinically positive axillary nodes either underwent radical mastectomy or underwent total mastectomy without axillary dissection but with postoperative irradiation. Kaplan-Meier and cumulative-incidence estimates of outcome were obtained. No significant differences were observed among the three groups of women with negative nodes or between the two groups of women with positive nodes with respect to disease-free survival, relapse-free survival, distant-disease-free survival, or overall survival. Among women with negative nodes, the hazard ratio for death among those who were treated with total mastectomy and radiation as compared with those who underwent radical mastectomy was 1.08 (95 percent confidence interval, 0.91 to 1.28; P=0.38), and the hazard ratio for death among those who had total mastectomy without radiation as compared with those who underwent radical mastectomy was 1.03 (95 percent confidence interval, 0.87 to 1.23; P=0.72). Among women with positive nodes, the hazard ratio for death among those who underwent total mastectomy and radiation as compared with those who underwent radical mastectomy was 1.06 (95 percent confidence interval, 0.89 to 1.27; P=0.49). The findings validate earlier results showing no advantage from radical mastectomy. Although differences of a few percentage points cannot be excluded, the findings fail to show a significant survival advantage from removing occult positive nodes at the time of initial surgery or from radiation therapy. Copyright 2002 Massachusetts Medical Society

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Brca1 breast tumors contain distinct CD44+/CD24- and CD133+ cells with cancer stem cell characteristics

Mollie Wright, Anna Maria Calcagno, Crystal Salcido … (2008)

Introduction Whether cancer stem cells occur in BRCA1-associated breast cancer and contribute to therapeutic response is not known. Methods We generated and characterized 16 cell lines from five distinct Brca1deficient mouse mammary tumors with respect to their cancer stem cell characteristics. Results All cell lines derived from one tumor included increased numbers of CD44+/CD24- cells, which were previously identified as human breast cancer stem cells. All cell lines derived from another mammary tumor exhibited low levels of CD44+/CD24- cells, but they harbored 2% to 5.9% CD133+ cells, which were previously associated with cancer stem cells in other human and murine tumors. When plated in the absence of attachment without presorting, only those cell lines that were enriched in either stem cell marker formed spheroids, which were further enriched in cells expressing the respective cancer stem cell marker. In contrast, cells sorted for CD44+/CD24- or CD133+ markers lost their stem cell phenotype when cultured in monolayers. As few as 50 to 100 CD44+/CD24- or CD133+ sorted cells rapidly formed tumors in nonobese diabetic/severe combined immunodeficient mice, whereas 50-fold to 100-fold higher numbers of parental or stem cell depleted cells were required to form few, slow-growing tumors. Expression of stem cell associated genes, including Oct4, Notch1, Aldh1, Fgfr1, and Sox1, was increased in CD44+/CD24- and CD133+ cells. In addition, cells sorted for cancer stem cell markers and spheroid-forming cells were significantly more resistant to DNA-damaging drugs than were parental or stem cell depleted populations, and they were sensitized to the drugs by the heat shock protein-90 inhibitor 17-DMAG (17-dimethylaminoethylamino-17-demethoxygeldanamycin hydrochloride). Conclusion Brca1-deficient mouse mammary tumors harbor heterogeneous cancer stem cell populations, and CD44+/CD24- cells represent a population that correlates with human breast cancer stem cells.

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EpCAM (CD326) finding its role in cancer

P Baeuerle, Olivier Gires (2007)

Although epithelial cell adhesion/activating molecule (EpCAM/CD326) is one of the first tumour-associated antigens identified, it has never received the same level of attention as other target proteins for therapy of cancer. It is also striking that ever since its discovery in the late 1970s the actual contribution of EpCAM to carcinogenesis remained unexplored until very recently. With a First International Symposium on EpCAM Biology and Clinical Application this is now changing. Key topics discussed at the meeting were the frequency and level of EpCAM expression on various cancers and its prognostic potential, the role of EpCAM as an oncogenic signalling molecule for cancer cells, recent progress on EpCAM-directed immunotherapeutic approaches in clinical development and the interaction of EpCAM with other proteins, which may provide a basis for a therapeutic window and repression of its growth-promoting signalling in carcinoma. Future research on EpCAM may benefit from a unified nomenclature and more frequent exchange among those who have been working on this cancer target during the past 30 years and will do so in the future.

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Author and article information

Contributors

Wei Wei

Hui Hu

Haosheng Tan

Louis WC Chow

Adrian YS Yip

Wings TY Loo

Conference

Journal ID (nlm-ta): J Transl Med

Journal ID (iso-abbrev): J Transl Med

Title: Journal of Translational Medicine

Publisher: BioMed Central

ISSN (Electronic): 1479-5876

Publication date Collection: 2012

Publication date (Electronic): 19 September 2012

Volume: 10

Issue: Suppl 1

Page: S6

Affiliations

[1 ]Department of Breast Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China

[2 ]Organisation for Oncology and Translational Research and UNIMED Medical Institute, Hong Kong, China

Article

Publisher ID: 1479-5876-10-S1-S6

DOI: 10.1186/1479-5876-10-S1-S6

PMC ID: 3445858

PubMed ID: 23046710

SO-VID: f23242d0-299f-4752-8c18-05b2527f4040

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Conference name: Organisation for Oncology and Translational Research (OOTR) 7th Annual Conference