Expression of ALDH1 in breast invasive ductal carcinoma: an independent predictor of early tumor relapse

Abstract

BackgroundThe 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.Methods147 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.ResultsALDH1A1-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).ConclusionsThe 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.

Proliferation rate and breast cancer subtype, but not ALDH1 expression, predict pathological response to neoadjuvant chemotherapy in locally advanced breast cancer

“…Schwartz et al [27] demonstrated epithelial and stromal ALDH1 expression in 17.3 and 42.3 % of breast cancers of Ghanaian women, whereas in non-malignant breast disease, epithelial and stromal ALDH1 expression was found in 15.9 and 58 %, respectively. These results contrast with those of other studies, which have shown a high frequency of ALDH1 expression only in invasive breast cancer [9]. Mieog et al [28] demonstrated that ALDH1 expression is age related and has prognostic significance.…”

“…However, there is limited and conflicting data available on its association with response to NACT. Persistence of ALDH1 positive cells in post NACT resection specimen is associated with poor overall survival [9].…”

Hypoxia induces the proliferation of endothelial progenitor cells via upregulation of Apelin/APLNR/MAPK signaling

“…Independent experiments were repeated three times. The relative expression levels of mRNA were analyzed using the 2 -∆∆Ct method (12).…”

Parthenolide inhibits LPS-induced inflammatory cytokines through the toll-like receptor 4 signal pathway in THP-1 cells

“…PCR was performed with 40 cycles on a Linegene real-time PCR detection system (Bioer Technology, Hangzhou, China) as follows: initial denaturation at 94°C for 3 min; denaturation at 94°C for 30 s; annealing at 60°C for 30 s; and extension at 72°C for 60 s. Finally, products were stained with ethidium bromide and electrophoresed through a 2% agarose gel. Data were analyzed using the 2 ÀΔΔCT method [16,17]. The level of TLR4 mRNA was normalized to that of GADPH mRNA.…”