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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

Isfoss, Björn Logi LU ; Holmqvist, Bo; Sand, Elin; Forsell, Johan; Jernström, Helena LU and Olsson, Håkan LU (2018) In BMC Cancer 18(1).
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.... (More)

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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organization
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type
Contribution to journal
publication status
published
subject
keywords
Aldehyde dehydrogenase, BRCA1, BRCA2, Breast, Breast cancer, Cancer risk, Familial cancer, Histology, Immunohistochemistry, Stem cells
in
BMC Cancer
volume
18
issue
1
publisher
BioMed Central
external identifiers
  • scopus:85042561967
ISSN
1471-2407
DOI
10.1186/s12885-018-4151-x
language
English
LU publication?
yes
id
62095fcf-33bd-495a-82c4-d1d58fbe6003
date added to LUP
2018-03-23 13:47:36
date last changed
2019-01-06 13:48:45
@article{62095fcf-33bd-495a-82c4-d1d58fbe6003,
  abstract     = {<p>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.</p>},
  articleno    = {230},
  author       = {Isfoss, Björn Logi and Holmqvist, Bo and Sand, Elin and Forsell, Johan and Jernström, Helena and Olsson, Håkan},
  issn         = {1471-2407},
  keyword      = {Aldehyde dehydrogenase,BRCA1,BRCA2,Breast,Breast cancer,Cancer risk,Familial cancer,Histology,Immunohistochemistry,Stem cells},
  language     = {eng},
  month        = {02},
  number       = {1},
  publisher    = {BioMed Central},
  series       = {BMC Cancer},
  title        = {Stellate cells and mesenchymal stem cells in benign mammary stroma are associated with risk factors for breast cancer - an observational study},
  url          = {http://dx.doi.org/10.1186/s12885-018-4151-x},
  volume       = {18},
  year         = {2018},
}