ORIGINAL ARTICLE
Aldehyde dehydrogenase-1 positivity is associated with ER negativity in patients with invasive ductal carcinoma of the breast
More details
Hide details
1
Department of Pathology, Batman State Hospital, Batman, Turkey
2
Department of Pathology, Near East University, Faculty of Medicine, Cyprus
3
Department of Pathology, University of Health Sciences, Bağcılar Traning and Research Hospital, Istanbul, Turkey
4
Department of General Surgery, University of Health Sciences, Bağcılar Training and Research Hospital, Istanbul, Turkey
Submission date: 2019-08-02
Final revision date: 2020-03-26
Acceptance date: 2020-04-27
Publication date: 2020-10-25
Pol J Pathol 2020;71(3):254-260
KEYWORDS
TOPICS
ABSTRACT
Cancer stem cells (CSCs) are self-renewable and can be differentiated into different cell types. They play an important role in oncogenic signaling pathways, tumor cell heterogeneity, metastasis, and therapeutic resistance. Aldehyde dehydrogenase 1
(ALDH1) was identified as a specific marker for breast CSCs. The study included a total of 105 patients with a diagnosis of invasive ductal carcinoma (IDC) who underwent mastectomy and with sufficient pathology material for histopathological examination. Patient demographics, tumor location, tumor diameter, the presence of lymphovascular and perineural invasion and lymph node metastasis, surgical margin status, and immunohistochemistry (IHC) staining results were obtained from patients’ records. The tumors were classified into IHC-based molecular subtypes according to the St. Gallen Consensus Conference in 2013. A four-tiered scoring system was used based on ALDH1 staining percentage in tumor cells. The tumor was determined as positive if the score was 2 or higher. Clinical, histopathological findings, and ALDH1 staining results were correlated. Twenty-five cases (23.8%) were ALDH1 positive. The ALDH1 positive group compared to the negative group was found to be associated with ER negativity (p = 0.044), but there was no correlation with other clinical and histopathological findings. ALDH1-positive IDCs may be less sensitive to hormonal therapy and associated with aggressive behavior.
REFERENCES (32)
1.
Meacham CE, Morrison SJ. Tumour heterogeneity and cancer cell plasticity. Nature 2013; 501: 328-337.
2.
Singh SK, Clarke ID, Terasaki M, et al. Identification of a cancer stem cell in human brain tumors. Cancer Res 2003; 63: 5821-5828.
3.
Diehn M, Cho RW, Lobo NA, et al. Association of reactive oxygen species levels and radioresistance in cancer stem cells. Nature 2009; 458: 780-783.
4.
Osborne CK, Yochmowitz MG, Knight WA, McGuire WL. The value of estrogen and progesterone receptors in the treatment of breast cancer. Cancer 1980; 46: 2884-2888.
5.
Lapidot T, Sirard C, Vormoor J, et al. A cell initiating human acute myeloid leukaemia after transplantation into SCID mice. Nature 1994; 367: 645-648.
6.
Al-Hajj M, Wicha MS, Benito-Hernandez A, et al. Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci 2003; 100: 3983-3988.
7.
Ginestier C, Hur MH, Charafe-Jauffret E, et al. 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.
8.
Rodriguez-Torres M, Allan AL. Aldehyde dehydrogenase as a marker and functional mediator of metastasis in solid tumors. Clin Exp Metastasis 2016; 33: 97-113.
9.
Vasiliou V, Nebert DW. Analysis and update of the human aldehyde dehydrogenase (ALDH) gene family. Hum Genomics 2005; 2: 138-143.
10.
Chute JP, Muramoto GG, Whitesides J, et al. Inhibition of aldehyde dehydrogenase and retinoid signaling induces the expansion of human hematopoietic stem cells. Proc Natl Acad Sci USA 2006; 103: 11707-11712.
11.
Jiang F, Qiu Q, Khanna A, et al. Aldehyde dehydrogenase 1 is a tumor stem cell-associated marker in lung cancer. Mol Cancer Res 2009; 7: 330-338.
12.
Croker AK, Allan AL. Inhibition of aldehyde dehydrogenase (ALDH) activity reduces chemotherapy and radiation resistance of stem-like ALDH hiCD44 + human breast cancer cells. Breast Cancer Res Treat 2012; 133: 75-87.
13.
Sugawara E, Nikaido H. Properties of AdeABC and AdeIJK efflux systems of Acinetobacter baumannii compared with those of the AcrAB-TolC system of Escherichia coli. Antimicrob Agents Chemother 2014; 58: 7250-7257.
14.
Hammond MEH, Hayes DF, Dowsett M, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in Breast Cancer. J Clin Oncol 2010; 28: 2784-2795.
15.
Wolff AC, Hammond MEH, Hicks DG, et al. Recommendations for human epidermal growth factor receptor 2 testing in breast cancer : American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update. J Clin Oncol 2013; 31: 3997-4013.
16.
Goldhirsch A, Winer EP, Coates AS, et al. Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann Oncol 2013; 24: 2206-2223.
17.
Kim SJ, Kim YS, Jang ED, et al. Prognostic Impact and Clinicopathological Correlation of CD133 and ALDH1 Expression in Invasive Breast Cancer. J Breast Cancer 2015; 18: 347.
18.
Bednarz-Knoll N, Nasta³y P, ¯aczek A, et al. Stromal expression of ALDH1 in human breast carcinomas indicates reduced tumor progression. Oncotarget 2015; 6: 26789-26803.
19.
Badowska-Kozakiewicz AM, Patera J, Sobol M, Przybylski J.
20.
The role of oestrogen and progesterone receptors in breast cancer – immunohistochemical evaluation of oestrogen and progesterone receptor expression in invasive breast cancer in women. Contemp Oncol (Poznan) 2015; 19: 220-225.
21.
Yoshioka T, Umekita Y, Ohi Y, et al. Aldehyde dehydrogenase 1 expression is a predictor of poor prognosis in node-positive breast cancers: a long-term follow-up study. Histopathology 2011; 58: 608-616.
22.
Resetkova E, Reis-Filho JS, Jain RK, et al. Prognostic impact of ALDH1 in breast cancer: a story of stem cells and tumor microenvironment. Breast Cancer Res Treat 2010; 123: 97-108.
23.
Deng S, Yang X, Lassus H, et al. Distinct expression levels and patterns of stem cell marker, aldehyde dehydrogenase isoform 1 (ALDH1), in human epithelial cancers. PLoS One 2010; 5: e10277.
24.
Charafe-Jauffret E, Ginestier C, Iovino F, et al. aldehyde dehydrogenase 1-positive cancer stem cells mediate metastasis and poor clinical outcome in inflammatory breast cancer. Clin Cancer Res 2010; 16: 45-55.
25.
Lv X, Wang Y, Song Y, et al. Association between ALDH1+/CD133+stem-like cells and tumor angiogenesis in invasive ductal breast carcinoma. Oncol Lett 2016; 11: 1750-1756.
26.
Park SY, Lee HE, Li H, et al. Heterogeneity for stem cell-related markers according to tumor subtype and histologic stage in breast cancer. Clin Cancer Res 2010; 16: 876-887.
27.
Pan H, Wu N, Huang Y, et al. Aldehyde dehydrogenase 1 expression correlates with the invasion of breast cancer. Diagn Pathol 2015; 10: 66.
28.
Ricardo S, Vieira AF, Gerhard R, et al. Breast cancer stem cell markers CD44, CD24 and ALDH1: Expression distribution within intrinsic molecular subtype. J Clin Pathol 2011; 64: 937-944.
29.
Neumeister V, Agarwal S, Bordeaux J, et al. In situ identification of putative cancer stem cells by multiplexing ALDH1, CD44, and cytokeratin identifies breast cancer patients with poor prognosis. Am J Pathol 2010; 176: 2131-2138.
30.
Mansour SF, Atwa MM. Clinicopathological significance of CD133 and ALDH1 cancer stem cell marker expression in invasive ductal breast carcinoma. Asian Pacific J Cancer Prev 2015; 16: 7491-7496.
31.
Heerma van Voss MR, van der Groep P, Bart J, et al. Expression of the stem cell marker ALDH1 in BRCA1 related breast cancer. Cell Oncol (Dordr) 2011; 34: 3-10.
32.
Honeth G, Lombardi S, Ginestier C, et al. Aldehyde dehydrogenase and estrogen receptor define a hierarchy of cellular differentiation in the normal human mammary epithelium. Breast Cancer Res 2014; 16: R52.