Expression of the Markers for the Mammary Stem Cells and the Cellular Lineages of the Mammary Gland on Ductal Carcinoma In Situ.
- Author:
Baik Hyeon JO
1
;
Hee Jung KIM
;
Yee Jeong KIM
;
Yangsoon PARK
;
Il Kyun LEE
;
Doy Il KIM
;
Won Hung LEE
;
Sei Ok YOON
Author Information
- Publication Type:Original Article
- Keywords: Heterogeneity; Target cells; ductal carcinoma in situ; Arrest of Differentiation
- MeSH: Actins; Biomarkers; Breast Neoplasms; Carcinoma, Ductal*; Carcinoma, Intraductal, Noninfiltrating*; Clone Cells; Cloning, Organism; Estrogens; Keratin-6; Mammary Glands, Human*; Population Characteristics; Receptors, Progesterone; Stem Cells*
- From:Journal of Breast Cancer 2006;9(3):184-192
- CountryRepublic of Korea
- Language:Korean
- Abstract: PURPOSE: Breast Cancer is an inter-tumoral and intra-tumoral heterogeneous disease. It remains unclear whether this heterogeneity results from different target cells or from different subsets of genetic abnormalities, otherwise from both. We postulated that in addition to genetic cloning, a variety of cells that exist during the defined developmental stages of the human mammary gland could give rise to the heterogeneity of breast cancer. To verify this postulation, we have analyzed pure ductal carcinoma in situ (DCIS) for the expression of the biomarkers that represent the mammary stem cell, the early progenitor cells, and the glandular and myoepithelial cells of the mammary gland. METHODS: We investigated the relationship between the immnuohistochemical expression of the mammary development-associated biomarkers {cytokeratin-18 (CK18), cytokeratin-6 (CK6), alpha-smooth muscle actin (SMA), Wnt-1, Notch 3} and some other factors {the menopausal status, the estrogen receptor (ER) status, the progesterone receptor (PR) status, c-erbB-2, and the number of tumor foci} in 26 cases of DCIS. RESULTS: All 26 cases included in this study showed the positive expressions of CK18 and SMA. The expression of all the markers was not correlated with the menopausal status. The positive expression of CK6 had a statistically significant relationship with a negative estrogen receptor (p=0.014), positive c-erbB-2 (p=0.048), high nuclear grade (p=0.001), and single focus of DCIS (p=0.017). The expression of Wnt-1 and Notch 3 did not have significant correlation with any factors. However, the positive expression of Wnt-1 showed a tendency of a negative ER (p=0.061) and the positive expression of Notch 3 also showed a tendency of a negative ER (p=0.086) and a high nuclear grade (p=0.086). CONCLUSION: The CK6 positive tumor is thought to originate from the more primitive cells compared to the CK6 negative tumor. Unifocality of the CK positive tumor might result from the arrest of differentiation of the original cell after disease affection. DCISs could be categorized into the CK6 positive and negative groups.
