良性乳腺基质中的星状细胞和间充质干细胞与乳腺癌的危险因素相关——一项观察性研究。
Stellate cells and mesenchymal stem cells in benign mammary stroma are associated with risk factors for breast cancer - an observational study.
机构信息
Department of Clinical Sciences, Lund, Division of Oncology and Pathology, Lund University, Lund, Sweden.
Department of Pathology, Skane University Hospital, Lund, Sweden.
出版信息
BMC Cancer. 2018 Feb 27;18(1):230. doi: 10.1186/s12885-018-4151-x.
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.
背景
目前尚不清楚良性乳腺组织中的基质细胞是否可以介导乳腺癌的风险。我们最近描述了绝经前女性形态正常的乳腺基质中醛脱氢酶 1 A1（ALDH1）阳性（+）细胞，数据表明其分布与乳腺癌的临床危险因素有关。本研究的目的是使用组织学和免疫组织化学方法定义这些细胞的身份，并研究这些细胞与绝经前和绝经后妇女的激素和遗传危险因素之间的关联。
方法
分析了 101 例特征明确的女性乳房手术切除的形态正常组织的基质。根据假定的干细胞标志物 ALDH1 和阶段特异性胚胎抗原 3（SSEA3）以及表明肥大细胞或星状细胞的免疫表型，应用形态学和免疫标记来确定细胞的身份。使用回归分析（双侧）将结果与患者的危险因素进行比较。
结果
BRCA1/2 携带者中 ALDH1+圆形/椭圆形细胞与低产次相关（p=0.022），而非 BRCA1/2 携带者中与不孕相关（p=0.057）。在绝经前妇女中，ALDH1+圆形/椭圆形细胞与家族史相关（p=0.058）。SSEA3+圆形/椭圆形细胞在形态学和免疫组织化学上与多谱系应激耐受（Muse）细胞一致，这些细胞与乳腺癌的危险因素独立相关，包括低产次（p=0.015）、家族史（p=0.021）和绝经后激素使用（p=0.032）。ALDH1+纺锤形/多边形细胞免疫组织化学上与星状细胞一致，与乳腺癌家族史呈负相关（p=0.001）。
结论
本研究鉴定了良性乳腺组织中的新型基质细胞类型，这些细胞有可能对女性进行乳腺癌风险分层。
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