PMID- 20228222
OWN - NLM
STAT- MEDLINE
DCOM- 20101215
LR  - 20211008
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Print)
IS  - 0002-9440 (Linking)
VI  - 176
IP  - 5
DP  - 2010 May
TI  - In situ identification of putative cancer stem cells by multiplexing ALDH1, CD44, 
      and cytokeratin identifies breast cancer patients with poor prognosis.
PG  - 2131-8
LID - 10.2353/ajpath.2010.090712 [doi]
AB  - A subset of cells, tentatively called cancer stem cells (CSCs), in breast cancer 
      have been associated with tumor initiation, drug resistance, and tumor 
      persistence or aggressiveness. They are characterized by CD44 positivity, CD24 
      negativity, and/or ALDH1 positivity in flow cytometric studies. We hypothesized 
      that the frequency or density of these cells may be associated with more 
      aggressive tumor behavior. We borrowed these multiplexed, flow-based methods to 
      develop an in situ method to define CSCs in formalin-fixed paraffin-embedded 
      breast cancer tissue, with the goal of assessing the prognostic value of the 
      presence of CSCs in breast cancer. Using a retrospective collection of 321 
      node-negative and 318 node-positive patients with a mean follow-up time of 12.6 
      years, we assessed TMAs using the AQUA method for quantitative 
      immunofluorescence. Using a multiplexed assay for ALDH1, CD44, and cytokeratin to 
      measure the coexpression of these proteins, putative CSCs appear in variable 
      sized clusters and in 27 cases (of 490), which showed significantly worse outcome 
      (log rank P = 0.0003). Multivariate analysis showed that this marker combination 
      is independent of tumor size, histological grade, nodal status, ER-, PR,- and 
      HER2-status. In this cohort, ALDH1 expression alone does not significantly 
      predict outcome. We conclude that the multiplexed method of in situ 
      identification of putative CSCs identifies high risk patients in breast cancer.
FAU - Neumeister, Veronique
AU  - Neumeister V
AD  - Department of Pathology, Yale University School of Medicine, New Haven, 
      Connecticut 06520-8023, USA.
FAU - Agarwal, Seema
AU  - Agarwal S
FAU - Bordeaux, Jennifer
AU  - Bordeaux J
FAU - Camp, Robert L
AU  - Camp RL
FAU - Rimm, David L
AU  - Rimm DL
LA  - eng
GR  - R33 CA110511/CA/NCI NIH HHS/United States
GR  - R33 CA 110511/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20100312
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (Hyaluronan Receptors)
RN  - 0 (Isoenzymes)
RN  - 68238-35-7 (Keratins)
RN  - EC 1.2.1 (Aldehyde Dehydrogenase 1 Family)
RN  - EC 1.2.1.3 (Aldehyde Dehydrogenase)
RN  - EC 1.2.1.36 (ALDH1A1 protein, human)
RN  - EC 1.2.1.36 (Retinal Dehydrogenase)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Aldehyde Dehydrogenase/*metabolism
MH  - Aldehyde Dehydrogenase 1 Family
MH  - Breast Neoplasms/*metabolism
MH  - Female
MH  - Gene Expression Profiling
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Hyaluronan Receptors/*metabolism
MH  - Isoenzymes/*metabolism
MH  - Keratins/*metabolism
MH  - Middle Aged
MH  - Neoplastic Stem Cells/*cytology
MH  - Prognosis
MH  - Retinal Dehydrogenase
MH  - Retrospective Studies
PMC - PMC2861079
EDAT- 2010/03/17 06:00
MHDA- 2010/12/16 06:00
PMCR- 2011/05/01
CRDT- 2010/03/16 06:00
PHST- 2010/03/16 06:00 [entrez]
PHST- 2010/03/17 06:00 [pubmed]
PHST- 2010/12/16 06:00 [medline]
PHST- 2011/05/01 00:00 [pmc-release]
AID - S0002-9440(10)60010-7 [pii]
AID - 10.2353/ajpath.2010.090712 [doi]
PST - ppublish
SO  - Am J Pathol. 2010 May;176(5):2131-8. doi: 10.2353/ajpath.2010.090712. Epub 2010 
      Mar 12.