Skip to main content
Erschienen in: Annals of Surgical Oncology 13/2012

01.12.2012 | Healthcare Policy and Outcomes

Expression Analysis of Aldehyde Dehydrogenase 1A1 (ALDH1A1) in Colon and Rectal Cancer in Association with Prognosis and Response to Chemotherapy

verfasst von: Christoph Kahlert, MD, Eva Gaitzsch, BA (hons), Gunnar Steinert, PhD, Carolin Mogler, MD, Esther Herpel, MD, Michael Hoffmeister, PhD, MSc, Lina Jansen, PhD, MSc, Axel Benner, MSc, Hermann Brenner, MD, MPH, Jenny Chang-Claude, PhD, MHS, Nuh Rahbari, MD, Thomas Schmidt, MD, Fee Klupp, MD, Niels Grabe, MD, Bernd Lahrmann, MSc, Moritz Koch, MD, Niels Halama, MD, Markus Büchler, MD, Juergen Weitz, MD, MSc

Erschienen in: Annals of Surgical Oncology | Ausgabe 13/2012

Einloggen, um Zugang zu erhalten

Abstract

Background

Aldehyde dehydrogenase 1A1 (ALDH1A1) has been described as a cancer stem cell marker and as a regulator of cellular chemoresistance. Therefore, ALDH1A1 has been suggested as potential biomarker to stratify patients into different risk categories for a “personalized” therapy approach. We have investigated the prognostic role of ALDH1A1 in primary colorectal cancer and its value in predicting response to chemotherapy in metastatic colorectal cancer.

Methods

Immunostaining against ALDH1A1 was performed on a paraffin-embedded tissue microarray including 659 primary colon cancer samples and 338 rectal cancer samples. Likewise, tissue of 44 palliatively resected colorectal liver metastases on whole-mount tissue slides was immunostained against ALDH1A1. Cytoplasmic, nuclear, and stromal expression of ALDH1A1 was assessed and merged with histopathological and clinical data.

Results

Univariate and multivariate analysis revealed that cytoplasmic and stromal expression of ALDH1A1 is not significantly associated with prognosis either in colon or in rectal cancer. Furthermore, cytoplasmic expression of ALDH1A1 does not predict response to palliative chemotherapy in patients with metastatic diseases. Intriguingly, as a novel finding, nuclear expression of ALDH1A1 was observed in a small subgroup of patients with colon cancer and rectal cancer. In colon cancer, nuclear expression was significantly associated with shortened overall survival by univariate and multivariate analysis.

Conclusions

Immunohistochemical expression analysis of ALDH1A1 in colon cancer is useful for the detection of nuclear expression in a small subpopulation of patients and is associated with shorter survival. Cytoplasmic expression fails to be of clinical relevance as prognostic or predictive marker in colorectal cancer.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.PubMedCrossRef Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.PubMedCrossRef
2.
Zurück zum Zitat Rahbari NN, Bork U, Motschall E, Thorlund K, Büchler MW, Koch M, et al. Molecular detection of tumor cells in regional lymph nodes is associated with disease recurrence and poor survival in node-negative colorectal cancer: a systematic review and meta-analysis. J Clin Oncol. 2012;30:60–70.PubMedCrossRef Rahbari NN, Bork U, Motschall E, Thorlund K, Büchler MW, Koch M, et al. Molecular detection of tumor cells in regional lymph nodes is associated with disease recurrence and poor survival in node-negative colorectal cancer: a systematic review and meta-analysis. J Clin Oncol. 2012;30:60–70.PubMedCrossRef
3.
Zurück zum Zitat Yoshida A, Rzhetsky A, Hsu LC, Chang C. Human aldehyde dehydrogenase gene family. Eur J Biochem. 1998;251:549–57.PubMedCrossRef Yoshida A, Rzhetsky A, Hsu LC, Chang C. Human aldehyde dehydrogenase gene family. Eur J Biochem. 1998;251:549–57.PubMedCrossRef
4.
Zurück zum Zitat Brenner H, Chang-Claude J, Seiler CM, Rickert A, Hoffmeister M. Protection from colorectal cancer after colonoscopy: a population-based, case-control study. Ann Intern Med. 2011;154:22–30.PubMed Brenner H, Chang-Claude J, Seiler CM, Rickert A, Hoffmeister M. Protection from colorectal cancer after colonoscopy: a population-based, case-control study. Ann Intern Med. 2011;154:22–30.PubMed
5.
Zurück zum Zitat Todaro M, Francipane MG, Medema JP, Stassi G. Colon cancer stem cells: promise of targeted therapy. Gastroenterology. 2010;138:2151–62.PubMedCrossRef Todaro M, Francipane MG, Medema JP, Stassi G. Colon cancer stem cells: promise of targeted therapy. Gastroenterology. 2010;138:2151–62.PubMedCrossRef
6.
Zurück zum Zitat Alison MR, Guppy NJ, Lim SM, Nicholson LJ. Finding cancer stem cells: are aldehyde dehydrogenases fit for purpose? J Pathol. 2010; 222:335–44.PubMedCrossRef Alison MR, Guppy NJ, Lim SM, Nicholson LJ. Finding cancer stem cells: are aldehyde dehydrogenases fit for purpose? J Pathol. 2010; 222:335–44.PubMedCrossRef
7.
Zurück zum Zitat Jiang F, Qiu Q, Khanna A, Todd NW, Deepak J, Xing L, et al. Aldehyde dehydrogenase 1 is a tumor stem cell-associated marker in lung cancer. Mol Cancer Res. 2009;7:330–8.PubMedCrossRef Jiang F, Qiu Q, Khanna A, Todd NW, Deepak J, Xing L, et al. Aldehyde dehydrogenase 1 is a tumor stem cell-associated marker in lung cancer. Mol Cancer Res. 2009;7:330–8.PubMedCrossRef
8.
Zurück zum Zitat Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, et al. ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell. 2007;1:555–67.PubMedCrossRef Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, et al. ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell. 2007;1:555–67.PubMedCrossRef
9.
Zurück zum Zitat Chang B, Liu G, Xue F, Rosen DG, Xiao L, Wang X, et al. ALDH1 expression correlates with favorable prognosis in ovarian cancers. Mod Pathol. 2009;22:817–23.PubMed Chang B, Liu G, Xue F, Rosen DG, Xiao L, Wang X, et al. ALDH1 expression correlates with favorable prognosis in ovarian cancers. Mod Pathol. 2009;22:817–23.PubMed
10.
Zurück zum Zitat Lugli A, Iezzi G, Hostettler I, Muraro MG, Mele V, Tornillo L, et al. Prognostic impact of the expression of putative cancer stem cell markers CD133, CD166, CD44s, EpCAM, and ALDH1 in colorectal cancer. Br J Cancer. 2010;103:382–90.PubMedCrossRef Lugli A, Iezzi G, Hostettler I, Muraro MG, Mele V, Tornillo L, et al. Prognostic impact of the expression of putative cancer stem cell markers CD133, CD166, CD44s, EpCAM, and ALDH1 in colorectal cancer. Br J Cancer. 2010;103:382–90.PubMedCrossRef
11.
Zurück zum Zitat Kahlert C, Bergmann F, Beck J, Welsch T, Mogler C, Herpel E, et al. Low expression of aldehyde dehydrogenase 1A1 (ALDH1A1) is a prognostic marker for poor survival in pancreatic cancer. BMC Cancer. 2011;11:275.PubMedCrossRef Kahlert C, Bergmann F, Beck J, Welsch T, Mogler C, Herpel E, et al. Low expression of aldehyde dehydrogenase 1A1 (ALDH1A1) is a prognostic marker for poor survival in pancreatic cancer. BMC Cancer. 2011;11:275.PubMedCrossRef
12.
Zurück zum Zitat Halama N, Zoernig I, Spille A, Westphal K, Schirmacher P, Jaeger D, et al. Estimation of immune cell densities in immune cell conglomerates: an approach for high-throughput quantification. PLoS One. 2009;4:7847.CrossRef Halama N, Zoernig I, Spille A, Westphal K, Schirmacher P, Jaeger D, et al. Estimation of immune cell densities in immune cell conglomerates: an approach for high-throughput quantification. PLoS One. 2009;4:7847.CrossRef
13.
Zurück zum Zitat Lahrmann B, Halama N, Sinn HP, Schirmacher P, Jaeger D, Grabe N. Automatic tumor-stroma separation in fluorescence TMAs enables the quantitative high-throughput analysis of multiple cancer biomarkers. PLoS One. 2011;6:28048.CrossRef Lahrmann B, Halama N, Sinn HP, Schirmacher P, Jaeger D, Grabe N. Automatic tumor-stroma separation in fluorescence TMAs enables the quantitative high-throughput analysis of multiple cancer biomarkers. PLoS One. 2011;6:28048.CrossRef
14.
Zurück zum Zitat Nedrebø BS, Søreide K, Eriksen MT, Dørum LM, Kvaløy JT, Søreide JA, et al. Survival effect of implementing national treatment strategies for curatively resected colonic and rectal cancer. Br J Surg. 2011;98:716–23.PubMedCrossRef Nedrebø BS, Søreide K, Eriksen MT, Dørum LM, Kvaløy JT, Søreide JA, et al. Survival effect of implementing national treatment strategies for curatively resected colonic and rectal cancer. Br J Surg. 2011;98:716–23.PubMedCrossRef
15.
Zurück zum Zitat Tweedle EM, Khattak I, Ang CW, Nedjadi T, Jenkins R, Park BK, et al. Low molecular weight heat shock protein HSP27 is a prognostic indicator in rectal cancer but not colon cancer. Gut. 2010;59:1501–10.PubMedCrossRef Tweedle EM, Khattak I, Ang CW, Nedjadi T, Jenkins R, Park BK, et al. Low molecular weight heat shock protein HSP27 is a prognostic indicator in rectal cancer but not colon cancer. Gut. 2010;59:1501–10.PubMedCrossRef
16.
Zurück zum Zitat Huang EH, Hynes MJ, Zhang T, Ginestier C, Dontu G, Appelman H, et al. Aldehyde dehydrogenase 1 is a marker for normal and malignant human colonic stem cells (SC) and tracks SC overpopulation during colon tumorigenesis. Cancer Res. 2009;69:3382–9.PubMedCrossRef Huang EH, Hynes MJ, Zhang T, Ginestier C, Dontu G, Appelman H, et al. Aldehyde dehydrogenase 1 is a marker for normal and malignant human colonic stem cells (SC) and tracks SC overpopulation during colon tumorigenesis. Cancer Res. 2009;69:3382–9.PubMedCrossRef
17.
Zurück zum Zitat Resetkova E, Reis-Filho JS, Jain RK, Mehta R, Thorat MA, Nakshatri H, et al. Prognostic impact of ALDH1 in breast cancer: a story of stem cells and tumor microenvironment. Breast Cancer Res Treat. 2010;123:97–108.PubMedCrossRef Resetkova E, Reis-Filho JS, Jain RK, Mehta R, Thorat MA, Nakshatri H, et al. Prognostic impact of ALDH1 in breast cancer: a story of stem cells and tumor microenvironment. Breast Cancer Res Treat. 2010;123:97–108.PubMedCrossRef
18.
Zurück zum Zitat Tanei T, Morimoto K, Shimazu K, Kim SJ, Tanji Y, Taguchi T, et al. Association of breast cancer stem cells identified by aldehyde dehydrogenase 1 expression with resistance to sequential paclitaxel and epirubicin-based chemotherapy for breast cancers. Clin Cancer Res. 2009;15:4234–41.PubMedCrossRef Tanei T, Morimoto K, Shimazu K, Kim SJ, Tanji Y, Taguchi T, et al. Association of breast cancer stem cells identified by aldehyde dehydrogenase 1 expression with resistance to sequential paclitaxel and epirubicin-based chemotherapy for breast cancers. Clin Cancer Res. 2009;15:4234–41.PubMedCrossRef
19.
Zurück zum Zitat Quash G, Fournet G, Chantepie J, Gore J, Ardiet C, Ardail D, et al. Novel competitive irreversible inhibitors of aldehyde dehydrogenase (ALDH1): restoration of chemosensitivity of L1210 cells overexpressing ALDH1 and induction of apoptosis in BAF(3) cells overexpressing bcl(2). Biochem Pharmacol. 2002;64:1279–92.PubMedCrossRef Quash G, Fournet G, Chantepie J, Gore J, Ardiet C, Ardail D, et al. Novel competitive irreversible inhibitors of aldehyde dehydrogenase (ALDH1): restoration of chemosensitivity of L1210 cells overexpressing ALDH1 and induction of apoptosis in BAF(3) cells overexpressing bcl(2). Biochem Pharmacol. 2002;64:1279–92.PubMedCrossRef
20.
Zurück zum Zitat Hilton J. Role of aldehyde dehydrogenase in cyclophosphamide-resistant L1210 leukemia. Cancer Res. 1984;44:5156–60.PubMed Hilton J. Role of aldehyde dehydrogenase in cyclophosphamide-resistant L1210 leukemia. Cancer Res. 1984;44:5156–60.PubMed
21.
Zurück zum Zitat Honoki K, Fujii H, Kubo A, Kido A, Mori T, Tanaka Y, et al. Possible involvement of stem-like populations with elevated ALDH1 in sarcomas for chemotherapeutic drug resistance. Oncol Rep. 2010;24:501–5.PubMedCrossRef Honoki K, Fujii H, Kubo A, Kido A, Mori T, Tanaka Y, et al. Possible involvement of stem-like populations with elevated ALDH1 in sarcomas for chemotherapeutic drug resistance. Oncol Rep. 2010;24:501–5.PubMedCrossRef
22.
Zurück zum Zitat Dylla SJ, Beviglia L, Park IK, Chartier C, Raval J, Ngan L, et al. Colorectal cancer stem cells are enriched in xenogeneic tumors following chemotherapy. PLoS One. 2008;3:2428.CrossRef Dylla SJ, Beviglia L, Park IK, Chartier C, Raval J, Ngan L, et al. Colorectal cancer stem cells are enriched in xenogeneic tumors following chemotherapy. PLoS One. 2008;3:2428.CrossRef
23.
Zurück zum Zitat Gazzaniga P, Gradilone A, Petracca A, Nicolazzo C, Raimondi C, Iacovelli R, et al. Molecular markers in circulating tumour cells from metastatic colorectal cancer patients. J Cell Mol Med. 2010;14:2073–7.PubMedCrossRef Gazzaniga P, Gradilone A, Petracca A, Nicolazzo C, Raimondi C, Iacovelli R, et al. Molecular markers in circulating tumour cells from metastatic colorectal cancer patients. J Cell Mol Med. 2010;14:2073–7.PubMedCrossRef
24.
Zurück zum Zitat Siebner H, Weber W. [Five years treatment of advanced solid malignomas with a combination of four cytostatic drugs (author’s transl)]. Osterr Z Onkol. 1976;3:8–26.PubMed Siebner H, Weber W. [Five years treatment of advanced solid malignomas with a combination of four cytostatic drugs (author’s transl)]. Osterr Z Onkol. 1976;3:8–26.PubMed
Metadaten
Titel
Expression Analysis of Aldehyde Dehydrogenase 1A1 (ALDH1A1) in Colon and Rectal Cancer in Association with Prognosis and Response to Chemotherapy
verfasst von
Christoph Kahlert, MD
Eva Gaitzsch, BA (hons)
Gunnar Steinert, PhD
Carolin Mogler, MD
Esther Herpel, MD
Michael Hoffmeister, PhD, MSc
Lina Jansen, PhD, MSc
Axel Benner, MSc
Hermann Brenner, MD, MPH
Jenny Chang-Claude, PhD, MHS
Nuh Rahbari, MD
Thomas Schmidt, MD
Fee Klupp, MD
Niels Grabe, MD
Bernd Lahrmann, MSc
Moritz Koch, MD
Niels Halama, MD
Markus Büchler, MD
Juergen Weitz, MD, MSc
Publikationsdatum
01.12.2012
Verlag
Springer-Verlag
Erschienen in
Annals of Surgical Oncology / Ausgabe 13/2012
Print ISSN: 1068-9265
Elektronische ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-012-2518-9

Weitere Artikel der Ausgabe 13/2012

Annals of Surgical Oncology 13/2012 Zur Ausgabe

Update Chirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

S3-Leitlinie „Diagnostik und Therapie des Karpaltunnelsyndroms“

CME: 2 Punkte

Prof. Dr. med. Gregor Antoniadis Das Karpaltunnelsyndrom ist die häufigste Kompressionsneuropathie peripherer Nerven. Obwohl die Anamnese mit dem nächtlichen Einschlafen der Hand (Brachialgia parästhetica nocturna) sehr typisch ist, ist eine klinisch-neurologische Untersuchung und Elektroneurografie in manchen Fällen auch eine Neurosonografie erforderlich. Im Anfangsstadium sind konservative Maßnahmen (Handgelenksschiene, Ergotherapie) empfehlenswert. Bei nicht Ansprechen der konservativen Therapie oder Auftreten von neurologischen Ausfällen ist eine Dekompression des N. medianus am Karpaltunnel indiziert.

Prof. Dr. med. Gregor Antoniadis
Berufsverband der Deutschen Chirurgie e.V.

S2e-Leitlinie „Distale Radiusfraktur“

CME: 2 Punkte

Dr. med. Benjamin Meyknecht, PD Dr. med. Oliver Pieske Das Webinar S2e-Leitlinie „Distale Radiusfraktur“ beschäftigt sich mit Fragen und Antworten zu Diagnostik und Klassifikation sowie Möglichkeiten des Ausschlusses von Zusatzverletzungen. Die Referenten erläutern, welche Frakturen konservativ behandelt werden können und wie. Das Webinar beantwortet die Frage nach aktuellen operativen Therapiekonzepten: Welcher Zugang, welches Osteosynthesematerial? Auf was muss bei der Nachbehandlung der distalen Radiusfraktur geachtet werden?

PD Dr. med. Oliver Pieske
Dr. med. Benjamin Meyknecht
Berufsverband der Deutschen Chirurgie e.V.

S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“

CME: 2 Punkte

Dr. med. Mihailo Andric
Inhalte des Webinars zur S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“ sind die Darstellung des Projektes und des Erstellungswegs zur S1-Leitlinie, die Erläuterung der klinischen Relevanz der Klassifikation EAES 2015, die wissenschaftliche Begründung der wichtigsten Empfehlungen und die Darstellung stadiengerechter Therapieoptionen.

Dr. med. Mihailo Andric
Berufsverband der Deutschen Chirurgie e.V.