Prognostic impact of the expression of putative cancer stem cell markers CD133, CD166, CD44s, EpCAM, and ALDH1 in colorectal cancer

Lugli, Alessandro; Iezzi, Giovanna; Hostettler, Isabel C.; Muraro, Manuele Giuseppe; Mele, Valentina; Tornillo, Luigi; Carafa, Vincenza; Spagnoli, Giulio C.; Terracciano, Luigi; Zlobec, Inti

doi:10.1038/sj.bjc.6605762

Cited by 269 publications

(281 citation statements)

References 47 publications

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“…In a review performed by Januchowski et al, the association between high level expression of ALDH1A1 and poor prognosis was shown in breast (Black et al, 2009;Tanei et al, 2009), bladder and prostate cancer patients (Li et al, 2010). It has also been shown to be a marker of CSCs in many types of solid tumors, including liver (Lingala et al, 2010), head and neck (Clay et al, 2010), pancreas (Rasheed et al, 2010), lung (Rasheed et al, 2010) ovary (Deng et al, 2010), and colon carcinomas (Lugli et al, 2010). Similar results were reported by Tanei et al in another study on breast cancer indicating the association between high expression of ALDH1A1 with lower overall survival and increase the number of ALDH1A1+ cells after chemptherapy (Tanei et al, 2009), since chemotherapy cannot eradicate cancer stem cells (CSCs) expressing ALDH1A1.…”

Section: Discussionmentioning

confidence: 99%

ALDH1 in Combination with CD44 as Putative Cancer Stem Cell Markers are Correlated with Poor Prognosis in Urothelial Carcinoma of the Urinary Bladder

Keymoosi¹,

Gheytanchi²,

Asgari³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Section: Discussionmentioning

confidence: 99%

ALDH1 in Combination with CD44 as Putative Cancer Stem Cell Markers are Correlated with Poor Prognosis in Urothelial Carcinoma of the Urinary Bladder

Keymoosi¹,

Gheytanchi²,

Asgari³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…In this study, we investigated two cancer stem-like cell/tumor-initiating cell markers. Aldehyde dehydrogenase 1(ALDH1) is a cytosolic isoform of ALDH, and high levels of its activity are seen not only in hematopoietic stem/ progenitor cells but also in solid cancers (eg, breast, 16,17 colorectal, 18 pancreas, 19 bladder 20 and prostate 21 cancers). Furthermore, expression of ALDH1 is a predictor of poor clinical outcome in the breast, 16,22 lung, 23 pancreatic 19 and bladder 20 cancers.…”

mentioning

confidence: 99%

Prognostic impact of the expression of ALDH1 and SOX2 in urothelial cancer of the upper urinary tract

et al. 2013

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Aldehyde dehydrogenase 1 (ALDH1) and sex determining region-Y-related high mobility group box 2 (SOX2) have been identified as putative cancer stem-like cell/tumor-initiating cell markers in various cancer tissues. The aim of this study was to elucidate the prognostic impact of these putative cancer stem-like cell/tumorinitiating cell markers in upper urinary tract urothelial cell carcinoma. Immunohistochemical staining for ALDH1 and SOX2 was carried out on archival specimens from 125 patients with upper urinary tract urothelial cell carcinoma who underwent radical nephroureterectomy. The prognostic value of ALDH1 and SOX2 expression and other clinicopathological features was evaluated. On univariate analysis, tumor grade, pathological T stage, pathological N stage, lymphovascular invasion, ALDH1 expression and SOX2 expression were associated with a poor prognosis. On multivariate analysis, the independent factors of prognosis were tumor grade (P ¼ 0.014), pathological N stage (P ¼ 0.005) and ALDH1 expression (P ¼ 0.002). In subgroup analysis, those subgroups with no positive, one positive or two positive results in immunohistochemistry for ALDH1 and SOX2 expression had estimated 5-year cancer-specific survival rates of 80%, 49% and 22%, respectively (Po0.001). Neither ALDH1 nor SOX2 expression correlated with intravesical recurrence after radical nephroureterectomy. These findings suggest that cancer stem-like cells/tumor-initiating cells are linked to more aggressive behavior of upper urinary tract urothelial cell carcinoma, supporting the current cancer stem cell hypothesis. Thus, therapeutic targeting of cancer stem-like cells/tumor-initiating cells in upper urinary tract urothelial cell carcinoma is a future possibility.

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“…The loss of adhesion molecules in CRC is reported to have an important role in the metastasis and invasion of tumors (4,6) and to be associated with a poor clinical outcome (5)(6)(7)(8). In addition, the loss of adhesion molecules is reported to be associated with resistance to chemotherapy (9).…”

Section: Introductionmentioning

confidence: 99%

Significance of E-cadherin and CD44 expression in patients with unresectable metastatic colorectal cancer

et al. 2017

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Abstract. The loss of adhesion molecules is reported to be associated with tumor invasion and metastasis in numerous types of cancer. Epithelial (E)-cadherin is an important molecule for cell-to-cell adhesion, while cluster of differentiation (CD)44 is an important molecule for cell-to-extracellular matrix adhesion. The focus of the present study was to evaluate the significance of the expression of E-cadherin and CD44 in patients with the unresectable metastatic colorectal cancer (CRC) who are undergoing palliative chemotherapy. Formalin-fixed, paraffin-embedded samples were obtained from 49 patients who underwent primary tumor resection and who were receiving palliative chemotherapy for unresectable metastatic CRC. The expression of E-cadherin and CD44 was evaluated using immunohistochemistry. The expression of E-cadherin was not significantly associated with progression-free survival (PFS; P=0.2825) or overall survival (OS; P=0.6617). The expression of CD44 was not associated with PFS (P=0.4365), but it did exhibit a certain level of association with OS (P=0.0699). However, the combined low expression of E-cadherin and CD44 demonstrated a significant association with decreased PFS (P=0.0101) and OS (P=0.0009). The combined loss of E-cadherin and CD44 expression also led to a reduction in the objective response rate and disease control rate (P=0.0076 and P=0.0294, respectively). A univariate analysis indicated that the combined low expression of E-cadherin and CD44 (P= 0.0474) and sex (P= 0.0330) were significantly associated with decreased PFS, and multivariate analysis confirmed combined low expression of E-cadherin and CD44 as an independent risk factor for decreased PFS [hazard ratio (HR), 8.276; 95% confidence interval (CI), 1.383-43.311; P=0.0227]. Univariate and multivariate analyses also indicated that the combined low expression of E-cadherin and CD44 expression was a significant prognostic factor for poor OS (HR, 15.118; 95% CI, 2.645-77.490; P=0.0039). Therefore the current study suggests that the combined low expression of E-cadherin and CD44 is an effective independent predictor of decreased chemotherapeutic outcome and survival in patients with unresectable metastatic CRC.

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Prognostic impact of the expression of putative cancer stem cell markers CD133, CD166, CD44s, EpCAM, and ALDH1 in colorectal cancer

Cited by 269 publications

References 47 publications

ALDH1 in Combination with CD44 as Putative Cancer Stem Cell Markers are Correlated with Poor Prognosis in Urothelial Carcinoma of the Urinary Bladder

ALDH1 in Combination with CD44 as Putative Cancer Stem Cell Markers are Correlated with Poor Prognosis in Urothelial Carcinoma of the Urinary Bladder

Prognostic impact of the expression of ALDH1 and SOX2 in urothelial cancer of the upper urinary tract

Significance of E-cadherin and CD44 expression in patients with unresectable metastatic colorectal cancer

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