| 1. |
- Isfoss, Björn
(author)
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Histologic characterization of stem cells in mammary epithelium and stroma
- 2017
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Doctoral thesis (other academic/artistic)abstract
- It is unknown whether native cells in benign breast tissue mediate risk of cancer.We therefore aimed to identify cell types in benign human mammary tissueimmunohistologically using markers of stemness and differentiation, and toinvestigate their possible associations with clinical risk factors for breast cancer.We found that cells that are integrated in benign epithelium and areimmunoreactive for the stem cell marker ALDH1 are negative for markers ofglandular differentiation, proliferation, and estrogen receptor. High numbers ofthese cells were associated with the risk factors family history of breast cancer,BRCA1/2 carrier status, low parity, and hormone use.Stromal ALDH1+ cells are either spindle-shaped/polygonal (s/p) or round/oval(r/o), and the latter are positive for the contractile protein marker SMMHC.ALDH1+ s/p cells are positive for the stellate cell marker vinculin. Low numbersof these cells were associated with family history, and when negative for the stemcell marker CD44 they were associated with nulliparity. Low numbers ofALDH1+ CD44+ CD24– r/o cells were associated with family history. ALDH1+r/o cells were positively or negatively associated with low parity depending on thepatients' BRCA1/2 status.High numbers of r/o cells that are positive for the mesenchymal stem cellmarker SSEA3 were associated with low parity, family history, and hormone useafter menopause.This study describes novel stromal cells in breast that were associated with riskfactors for breast cancer. If confirmed in independent cohorts, they may be usedfor stratification of women with regard to risk of breast cancer.
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| 2. |
- Isfoss, Björn Logi, et al.
(author)
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Stellate cells and mesenchymal stem cells in benign mammary stroma are associated with risk factors for breast cancer - an observational study
- 2018
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In: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 18:1
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Journal article (peer-reviewed)abstract
- Background: It is not known whether stromal cells in benign breast tissue can mediate risk of breast cancer. We recently described aldehyde dehydrogenase 1 A1 (ALDH1) positive (+) cells in morphologically normal breast stroma of premenopausal women, and the data indicated that their distribution is associated with clinical risk factors for breast cancer. The aim of the present study was to define the identities of these cells using histologic and immunohistologic methods, and to investigate associations between those cells and hormonal and genetic risk factors in pre- and postmenopausal women. Methods: Stroma of morphologically normal tissue was analyzed in samples from 101 well-characterized women whose breasts had been operated. Morphology and immunolabeling were applied to determine cell identities based on the putative stem cell markers ALDH1 and stage-specific embryonic antigen-3 (SSEA3), and immunophenotypes indicating mast cells or stellate cells. The results were compared with the patients' risk factors using regression analysis (two-tailed). Results: ALDH1+ round/oval cells were associated with low parity in BRCA1/2 carriers (p=0.022), while in non-BRCA1/2-carriers they were negatively associated with nulliparity (p=0.057). In premenopausal women ALDH1+ round/oval cells were associated with family history (p=0.058). SSEA3+ round/oval cells were morphologically and immunohistologically consistent with multilineage stress-enduring (Muse) cells, and these cells were independently associated with the breast cancer risk factors low parity (p=0.015), family history (p=0.021), and hormone use after menopause (p=0.032). ALDH1+ spindle-shaped/polygonal cells were immunohistologically consistent with stellate cells, and were negatively associated with family history of breast cancer (p=0.001). Conclusion: This study identified novel stromal cell types in benign breast tissue that have a potential for stratifying women for breast cancer risk.
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| 3. |
- Isfoss, Björn Logi, et al.
(author)
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The absence of aldehyde dehydrogenase 1 A1-positive cells in benign mammary stroma is associated with risk factors for breast cancer
- 2016
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In: Breast Cancer: Targets and Therapy. - 1179-1314. ; 8, s. 117-124
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Journal article (peer-reviewed)abstract
- In this study, aldehyde dehydrogenase 1 (ALDH1)-expressing cells in stroma of histologically normal breast tissue from premenopausal women were investigated in situ regarding cellular morphology, cell distribution, and relation to the additional stem cell markers, CD44 (+) and CD24 (-). These results were correlated with hormonal and genetic risk factors for breast cancer. Triple immunofluorescence labeling was performed on tissues from premenopausal women with a family history of breast cancer, and breast reduction specimens from premenopausal women with no family history of breast cancer were used as a control group. The majority of ALDH1-immunoreactive cells in stroma were spindle-shaped or polygonal, and such cells that were CD44- and CD24- were absent in the breast stroma of a significantly larger number of nulliparous than parous women. A less common morphological type of ALDH1-positive cells in stroma was round or oval in shape, and such cells that were CD44+ and CD24- were absent in a significant number of women with a family history of breast cancer. The CD44+/CD24- immunophenotype is consistent with stem cells, and the round/oval morphology suggests mesenchymal cells. This study demonstrates that there are two morphologically distinct types of ALDH1-positive cells in histologically benign mammary stroma, and the absence of these cells is correlated with clinical risk factors for breast cancer in premenopausal women.
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