title: 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.
authors.affiliation: Department of Breast and Endocrine Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Masami
authors.initials: M
authors.lastname: Tsukabe
authors.forename: Kenzo
authors.initials: K
authors.lastname: Shimazu
authors.forename: Koji
authors.initials: K
authors.lastname: Morimoto
authors.forename: Yasuto
authors.initials: Y
authors.lastname: Naoi
authors.forename: Naofumi
authors.initials: N
authors.lastname: Kagara
authors.forename: Masafumi
authors.initials: M
authors.lastname: Shimoda
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shimomura
authors.forename: Naomi
authors.initials: N
authors.lastname: Maruyama
authors.forename: Seung Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Shinzaburo
authors.initials: S
authors.lastname: Noguchi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000080924:Aldehyde Dehydrogenase 1 Family; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000201:enzymology* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000201:enzymology*; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D050697:Retinal Dehydrogenase / Q000378:metabolism*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D007527:Isoenzymes; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase