ALDH1 expression indicates chemotherapy resistance and poor outcome in node-negative rectal cancer
ALDH1 expression indicates chemotherapy resistance and poor outcome in node-negative rectal cancer
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DOI：
10.1016/j.humpath.2012.10.003
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发表时间：
2013-06-01
期刊：
影响因子：
3.3
通讯作者：
Sundstrom, Jari T. T.
中科院分区：
文献类型：
--
作者：
Avoranta, S. Tuulia;Korkeila, Eija A.;Sundstrom, Jari T. T.
癌症干细胞标志物乙醛脱氢酶1（ALDH 1）与几种人类癌症的治疗抗性和不良后果有关。我们研究了ALDH 1在直肠癌中的表达，特别强调了其与治疗反应和疾病结局的关系。对64例活检和209例手术样本进行了ALDH 1的免疫组织化学染色，这些样本来自接受短程（n = 89）或长期（n = 46）（化疗）放疗加手术或仅手术（n = 74）治疗的直肠癌患者。将染色结果与临床病理变量、肿瘤消退等级（TRG）和疾病结局进行比较。分析了197例手术标本的细胞核β-连环蛋白表达模式。149例手术样本（71%）中存在ALDH 1阳性表达，与细胞核β-连环蛋白调节缺陷相关（P = 0.018）。在相应的活检和手术样本的成对比较中，在大多数病例中，ALDH 1表达在术前（化疗）放疗后保持稳定或增加，而仅在少数病例中降低（阳性/阴性类别P = 0.02;强度P <0.001）。然而，ALDH 1表达与肿瘤消退等级无关。在淋巴结阴性直肠癌中，ALDH 1表达是短期无病生存期和疾病特异性生存期的独立预测因子（P = 0.044; P = 0.049），特别是在接受辅助化疗的患者中。我们的结论是ALDH 1与β-连环蛋白信号失调有关，支持ALDH 1在直肠癌干性中的作用。ALDH 1表达与早期直肠癌预后不良有关，这是一个特别需要新的预后工具的群体，并可能表明化疗和放射抗性。(C)2013 Elsevier Inc. All rights reserved.
The cancer stem cell marker aldehyde dehydrogenase 1 (ALDH1) associates with treatment resistance and adverse outcome in several human cancers. We studied ALDH1 expression in rectal cancer, with special emphasis on its association with treatment response and disease outcome Immunohistochemical staining for ALDH1 was conducted for 64 biopsies and 209 operative samples from rectal cancer patients treated with short- (n = 89) or long:course (n = 46) (chemo)radiotherapy plus surgery, or with surgery only (n = 74). The staining results were compared to clinicopathological variables, tumor regression grade (TRG) and disease outcome. Nuclear beta-catenin expression pattern was analyzed from 197 operative samples. Positive ALDH1 expression was present in 149 operative samples (71%), correlating with deficient nuclear beta-catenin regulation (P = .018). In a pairwise comparison of respective biopsy and operative samples, ALDH1 expression remained stable or increased after preoperative (chemo)radiotherapy in most of the cases, while it decreased in few cases only (P = .02 for positive/negative category; P < .001 for intensity). ALDH1 expression did not, however, relate to tumor regression grade. In node-negative rectal cancer, ALDH1 expression was an independent predictor of short disease-free and disease-specific survival (P = .044; P = .049), specifically among patients treated with adjuvant chemotherapy. We conclude that ALDH1 associates with deregulated beta-catenin signaling, supporting the role of ALDH1 in rectal cancer sternness. ALDH1 expression relates to poor outcome in early stage rectal cancer, a group where new prognostic tools are particularly needed, and may indicate chemo- and radioresistance. (C) 2013 Elsevier Inc. All rights reserved.