Department of Breast Disease, Peking Union Medical College Hospital, Peking Union Medical College, Beijing, 100730, China.
Cancer Cell Int. 2013 Jun 15;13(1):60. doi: 10.1186/1475-2867-13-60.
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.
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.
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).
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.
醛脱氢酶 1（ALDH1）表型对乳腺癌转移行为和早期肿瘤复发的具体作用机制尚不清楚。
对 147 例随机选择的浸润性导管癌样本进行 ALDH1A1、NOTCH1、雌激素受体（ER）、孕激素受体（PR）和人表皮生长因子受体（HER2）的表达检测，并进一步评估 ALDH1A1 表型与临床病理特征的关系。
在 147 例肿瘤中检测到 ALDH1A1 阳性细胞 63.3%（93/147）。强 ALDH1A1 染色的 80.0%（32/40）肿瘤表现为早期复发，而 ALDH1A1 阴性的肿瘤为 20.0%（8/40）（P=0.027）。ALDH1A1 状态与强恶性增殖标志物 Ki67 染色显著相关（P=0.001），并且在 ER、PR 和 HER2 表达的亚型以及肿瘤组织的三阴性特征中，ALDH1A1 的表达无显著差异。多变量回归分析表明，升高的 ALDH1A1 表达是无复发生存和无远处转移生存的独立预测因子。值得注意的是，与 ALDH1A1 弱肿瘤组织相比，ALDH1A1 表达强的乳腺癌组织 NOTCH1 染色较弱（P=0.002），并且 ALDH1A1 和 NOTCH1 mRNA 阳性之间存在显著关系（Pearson 相关系数-0.337，P=0.014；Spearman's rho-0.376，P=0.006）。升高的 NOTCH1 mRNA 水平（基于中位数 ALDH1A1 2-△△CT 值的截断值）与 ALDH1A1 mRNA 水平的降低相关（P=0.001）。
ALDH1A1 表型是浸润性导管癌早期肿瘤复发特征（具体为早期局部复发和远处转移的发生率）的独立预测因子。NOTCH1 信号通路可能参与了 ALDH1A1 表型与浸润性导管癌早期恶性复发的负相关。
