Clinicopathological Analysis of Breast Ductal Carcinoma in situ with ALDH1-Positive Cancer Stem Cells

Abstract

Objective: The aim of this study was to elucidate the clinicopathological characteristics of breast ductal carcinomas in situ (DCIS) with aldehyde dehydrogenase 1 (ALDH1)-positive cancer stem cells (CSCs). Methods: DCIS (n = 194) were subjected to immunohistochemical staining and results were examined for associations with various clinicopathological parameters. The ALDEFLUOR assay for breast cancer cell lines was also performed to determine the proportion of CSCs according to intrinsic subtype. Results: DCIS with ALDH1-positive CSCs were significantly (p < 0.05) more likely to be estrogen receptor-α (ER)-negative, progesterone receptor (PgR)-negative, Ki67-positive and HER2-positive tumors. Luminal A subtype (8.6%) showed a significantly (p < 0.001) lower ALDH1 positivity than the other subtypes [luminal B (50.0%), luminal HER2 (36.8%), HER2 (35.3%) and triple-negative subtype (26.7%)]. Double immunostaining revealed that ALDH1-positive CSCs did not overlap with ER-, PgR- or Ki67-positive tumor cells but did overlap with HER2-positive tumor cells. The percentage of ALDEFLUOR-positive CSCs was lower in the luminal A cell lines (0.02% for T-47D and 0.4% for MCF7) than in the luminal HER2 (9.1% for BT-474 and 9.5% for MDA-MB-361), HER2 (13.9% for AU565 and 33.2% for SK-BR-3) and triple-negative cell lines (28.4% for MDA-MB-231 and 30.7% for MDA-MB-468). Conclusions: Our results suggest that most CSCs in DCIS are in the G0 phase (Ki67 negative) and do not express ER or PgR, but they do express HER2 in HER2-positive tumors.

Quantitative assessment of cold atmospheric plasma anti‐cancer efficacy in triple‐negative breast cancers

“…Second, cancer stem cell model. As TN breast cancer cells have more percentage of cancer stem cells than the other subtypes, we have good excuses to expect and assume that PAM is more effective in killing cancer stem cells. This feature, once true, makes PAM a promising oncotherapeutic approach as it may eradicate cancer stem cells that is the source of metastasis and relapse.…”

Functional Antagonism of Junctional Adhesion Molecule-A (JAM-A), Overexpressed in Breast Ductal Carcinoma In Situ (DCIS), Reduces HER2-Positive Tumor Progression

“…Independence from exogenous estrogen is unsurprising given the ER-negativity of SUM-225 cells, but an asset in the sense that slow-growing murine tumors of this nature may better represent indolent DCIS tumors than models requiring supplementation with supraphysiological estrogen levels. Furthermore, since coincident ER-negativity/HER2-positivity in DCIS patients has been associated with larger tumors and increased recurrence rates [ 33 ], in addition to cancer stem cell enrichment [ 34 ], the subset of DCIS patients represented by SUM-225 cells has greater need of new drug targets than the majority of DCIS patients with low-risk ER-positive disease.…”

Heterogeneity of BCSCs contributes to the metastatic organotropism of breast cancer

“…Based on immunohistochemistry analysis of CD24 and CD44 expression in 50 breast cancer patients, Idowu MO also suggested that CD24-CD44+ BCSCs played a significant role in triple negative subtype of breast cancer [ 39 ]. In addition, Tsukabe M found that ALDH+ BCSCs were more likely to overlap with HER2-positive tumor cells while luminal A subtype displayed low ALDH1 activities [ 36 ]. Similar with Tsukabe M, Park SY discovered that the frequency of ALDH1-positive cells was higher in HER2+ breast tumors than luminal breast tumors [ 37 ].…”