Clinicopathologic Characteristics of Breast Cancer Stem Cells Identified on the Basis of Aldehyde Dehydrogenase 1 Expression

다국어 초록 (Multilingual Abstract)

Purpose: Breast cancer displays varying molecular and clinicalfeatures. The ability to form breast tumors has been shown byseveral studies with aldehyde dehydrogenase 1 (ALDH1) positivecells. The aim of this study is to investigate the association betweenALDH1 expression and clinicopathologic characteristics ofinvasive ductal carcinoma. Methods: We investigated breast cancertissues for the prevalence of ALDH1+ tumor cells and theirprognostic value. The present study included paraffin-embeddedtissues of 70 patients with or without recurrences. We appliedimmunohistochemical staining for the detection of ALDH1+ cells.
Analysis of the association of clinical outcomes and molecularsubtype with marker status was conducted. Results: ALDH1+and ALDH1– tumors were more frequent in triple-negative breastcancers and in luminal A breast cancers, respectively (p<0.01).
ALDH1 expression was found to exert significant impact on diseasefree survival (DFS) (ALDH1+ vs. ALDH1–, 53.1±6.7 monthsvs. 79.2±4.7 months; p=0.03) and overall survival (OS) (ALDH1+vs. ALDH1–, 68.5±4.7 months vs. 95.3±1.1 months; p<0.01). Intriple-negative breast cancer (TNBC) patients, DFS and OSshowed no statistical differences according to ALDH1 expression(ALDH1+ vs. ALDH1–, 45.3±9.4 months vs. 81.3±7.4 months,p=0.52; 69.0±7.5 months vs. 91.3±6.3 months, p=0.67). However,non-TNBC patients showed significant OS difference betweenALDH1+ and ALDH1– tumors (ALDH1+ vs. ALDH1–, 77.6±3.6 months vs. 98.0±1.0 months; p=0.04) with no statistical differenceof DFS (ALDH1+ vs. ALDH1–, 60.5±8.0 months vs. 81.8±4.6 months; p=0.27). Conclusion: Our findings suggest that theexpression of ALDH1 in breast cancer may be associated withTNBC and poor clinical outcomes. On the basis of our findings,we propose that ALDH1 expression in breast cancer could becorrelated with poor prognosis, and may contribute to a moreaggressive cancer phenotype.

참고문헌 (Reference)

1 Mylona E, "The clinicopathologic and prognostic significance of CD44+/CD24(-/low) and CD44-/CD24+ tumor cells in invasive breast carcinomas" 39 : 1096-1102, 2008

2 Honeth G, "The CD44+/CD24- phenotype is enriched in basallike breast tumors" 10 : R53-, 2008

3 Reya T, "Stem cells, cancer, and cancer stem cells" 414 : 105-111, 2001

4 Guler G, "Stem cell-related markers in primary breast cancers and associated metastatic lesions" 25 : 949-955, 2012

5 Sorlie T, "Repeated observation of breast tumor subtypes in independent gene expression data sets" 100 : 8418-8423, 2003

6 Al-Hajj M, "Prospective identification of tumorigenic breast cancer cells" 100 : 3983-3988, 2003

7 Allred DC, "Prognostic and predictive factors in breast cancer by immunohistochemical analysis" 11 : 155-168, 1998

8 Neumeister V, "In situ identification of putative cancer stem cells by multiplexing ALDH1, CD44, and cytokeratin identifies breast cancer patients with poor prognosis" 176 : 2131-2138, 2010

9 Perrone G, "In situ identification of CD44+/CD24- cancer cells in primary human breast carcinomas" 7 : e43110-, 2012

10 Currie MJ, "Immunohistochemical analysis of cancer stem cell markers in invasive breast carcinoma and associated ductal carcinoma in situ:relationships with markers of tumor hypoxia and microvascularity" 44 : 402-411, 2013

11 Park SY, "Heterogeneity for stem cell-related markers according to tumor subtype and histologic stage in breast cancer" 16 : 876-887, 2010

12 Sorlie T, "Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications" 98 : 10869-10874, 2001

13 임성직, "Clinicopathological Significance of Invasive Ductal Carcinoma with High Prevalence of CD44+/CD24-/low Tumor Cells in Breast Cancer" 대한병리학회 44 (44): 390-396, 2010

14 Bane A, "Clinical-pathologic significance of cancer stem cell marker expression in familial breast cancers" 140 : 195-205, 2013

15 de Beça FF, "Cancer stem cells markers CD44, CD24 and ALDH1 in breast cancer special histological types" 66 : 187-191, 2013

16 Takahashi RU, "Cancer stem cells in breast cancer" 3 : 1311-1328, 2011

17 Jordan CT, "Cancer stem cells" 355 : 1253-1261, 2006

18 Lin Y, "CD44+/CD24- phenotype contributes to malignant relapse following surgical resection and chemotherapy in patients with invasive ductal carcinoma" 31 : 59-, 2012

19 Sun H, "CD44+/CD24- breast cancer cells isolated from MCF-7 cultures exhibit enhanced angiogenic properties" 15 : 46-54, 2013

20 Sheridan C, "CD44+/CD24- breast cancer cells exhibit enhanced invasive properties: an early step necessary for metastasis" 8 : R59-, 2006

21 Idowu MO, "CD44(+)/CD24(-/low) cancer stem/progenitor cells are more abundant in triple-negative invasive breast carcinoma phenotype and are associated with poor outcome" 43 : 364-373, 2012

22 Ricardo S, "Breast cancer stem cell markers CD44, CD24 and ALDH1: expression distribution within intrinsic molecular subtype" 64 : 937-946, 2011

23 Tanei T, "Association of breast cancer stem cells identified by aldehyde dehydrogenase 1 expression with resistance to sequential paclitaxel and epirubicin-based chemotherapy for breast cancers" 15 : 4234-4241, 2009

24 Ginestier C, "ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome" 1 : 555-567, 2007

25 Douville J, "ALDH1 as a functional marker of cancer stem and progenitor cells" 18 : 17-25, 2009