title: Aldehyde dehydrogenase1 immunohistochemical staining in primary breast cancer cells independently predicted overall survival but did not correlate with the presence of circulating or disseminated tumors cells.
abstract: OBJECTIVE
  We hypothesized that aldehyde dehydrogenase 1 (ALDH1) staining in breast cancer tumor cells might be a simple surrogate for the presence of circulating tumor cells (CTCs) or disseminated tumor cells (DTCs).
  
  
  METHODS
  Whole tissue primary tumor sections from 121 patients enrolled in a clinical trial assessing CTCs and DTCs at the time of surgery were stained for ALDH1 and scored by a dedicated breast pathologist blinded to outcome. Clinical data was extracted and staining was correlated to clinical variables and outcome by Fisher's exact test, the Log rank test and Cox proportional hazards regression analysis respectively. P < 0.05 was considered significant.
  
  
  RESULTS
  ALDH1 staining in tumor cells was present in 12% of cases (15/121). In univariate analysis, ALDH1 tumor staining predicted worse overall survival (71% vs. 91% at 5 years P = 0.0074) and was an independent predictor on multivariable analysis of worse overall survival, (HR 4.93) after adjusting for stage, ER, grade, LVI, age and neoadjuvant chemotherapy (P = 0.04). ALDH1 was significantly associated with estrogen receptor (ER) negative (P value = 0.029) primary tumors but not the presence of CTCs or DTCs by multivariate logistic regression. Positive ALDH staining in non-tumor cells of any pattern or morphology was common but did not correlate with CTCs or DTCs, other clinical variables, or outcome.
  
  
  CONCLUSIONS
  ALDH1 tumor staining was associated with ER -negative breast cancer and was an independent predictor of OS. However, it did not correlate to putative cancer stem cell surrogates CTCs and/or DTCs.
authors.affiliation: 1. Departments of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, 77030;
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Woodward
authors.affiliation: 2. Departments of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, 77030;
authors.forename: Savitri
authors.initials: S
authors.lastname: Krishnamurthy
authors.affiliation: 3. Departments of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, 77030;
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Lodhi
authors.affiliation: 4. Departments of Biostatistics, The University of Texas M.D. Anderson Cancer Center, Houston, TX, 77030;
authors.forename: Lianchun
authors.initials: L
authors.lastname: Xiao
authors.affiliation: 2. Departments of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, 77030;
authors.forename: Yun
authors.initials: Y
authors.lastname: Gong
authors.affiliation: 5. The Department of Medical Oncology Thomas Jefferson University.
authors.forename: Massimo
authors.initials: M
authors.lastname: Cristofanilli
authors.affiliation: 1. Departments of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, 77030;
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Buchholz
authors.affiliation: 3. Departments of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, 77030;
authors.forename: Anthony
authors.initials: A
authors.lastname: Lucci
keywords: ALDH1; breast cancer; cancer stem cells; circulating tumor cells; disseminated tumor cells; micrometastatic disease.