title: Expression of ALDH1 in breast invasive ductal carcinoma: an independent predictor of early tumor relapse.
abstract: BACKGROUND
  The specific mechanism underlying the contribution of the Aldehyde dehydrogenase 1 (ALDH1) phenotype to metastatic behavior and early tumor relapse in breast cancer is currently unclear.
  
  
  METHODS
  147 randomly selected invasive ductal carcinoma samples were assayed for expression of ALDH1A1, NOTCH1, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2), and association of the ALDH1A1 phenotype with clinic pathological features was further evaluated.
  
  
  RESULTS
  ALDH1A1-positive cells were detected in 63.3% (93 of 147) of tumors. 80.0% (32 of 40) of tumors with strong ALDH1A1 staining displayed early recurrence, compared with 20.0% (8 of 40) of tumors negative for ALDH1A1 expression (P = 0.027). ALDH1A1 status was significantly correlated with strong malignant proliferative marker Ki67 staining (P = 0.001), and no significantly different expression of ALDH1A1 across the subtypes of ER, PR, and HER2 expression and triple negative features of tumor tissue. Multivariate regression analysis demonstrated that elevated ALDH1A1 expression is an independent predictor of recurrence-free survival and distant metastasis-free survival. Notably, breast cancer tissue strong for ALDH1A1 expression displayed weak NOTCH1 staining compared to ALDH1A1 weak tumor tissue (P = 0.002), and the relationship between ALDH1A1 and NOTCH1 mRNA positivity was significant (Pearson correlation - 0.337, P = 0.014; Spearman's rho - 0.376, P = 0.006). Elevated NOTCH1 mRNA level (using a cut-off value based on the median ALDH1A1 2-△△CT value) was associated with reduction of ALDH1A1 mRNA level (P = 0.001).
  
  
  CONCLUSIONS
  The ALDH1A1 phenotype is an independent predictor of early tumor relapse characteristic (specifically, incidence of early local recurrence and distant metastasis) of invasive ductal carcinoma. The NOTCH1 signaling pathway is possibly involved in the negative association of the ALDH1A1 phenotype with early malignant relapse in invasive ductal carcinoma.
authors.affiliation: Department of Breast Disease, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, 100730, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: Department of Breast Disease, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, 100730, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Breast Disease, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, 100730, China.
authors.forename: Songjie
authors.initials: S
authors.lastname: Shen
authors.affiliation: Department of Breast Disease, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, 100730, China.
authors.forename: Yidong
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Breast Disease, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, 100730, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Mao
authors.affiliation: Department of Breast Disease, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, 100730, China.
authors.forename: Jinghong
authors.initials: J
authors.lastname: Guan
authors.affiliation: Department of Breast Disease, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, 100730, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Sun