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Open Access Highly Accessed Research article

Low expression of aldehyde deyhdrogenase 1A1 (ALDH1A1) is a prognostic marker for poor survival in pancreatic cancer

Christoph Kahlert1*, Frank Bergmann2, Janine Beck1, Thilo Welsch1, Carolin Mogler2, Esther Herpel2, Shamik Dutta1, Thomas Niemietz1, Moritz Koch1 and Jürgen Weitz1

Author Affiliations

1 Department of General, Visceral and Transplantation Surgery, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany

2 Institute of Pathology, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany

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BMC Cancer 2011, 11:275  doi:10.1186/1471-2407-11-275

Published: 27 June 2011

Abstract

Background

Aldehyde deyhdrogenase 1 (ALDH1) has been characterised as a cancer stem cell marker in different types of tumours. Additionally, it plays a pivotal role in gene regulation and endows tumour cells with augmented chemoresistance. Recently, ALDH1A1 has been described as a prognostic marker in a pancreatic cancer tissue microarray. The aim of this study was to reevaluate the expression of ALDH1A1 as a prognostic marker on whole-mount tissue sections.

Methods

Real-time-quantitative-PCR (qRT-PCR) and Western blotting were used to evaluate the expression profile of ALDH1A1 in seven pancreatic cancer cell lines and one non-malignant pancreatic cell line. Immunostaining against ALDH1A1 and Ki-67 was performed on paraffin-embedded samples from 97 patients with pancreatic cancer. The immunohistochemical results were correlated to histopathological and clinical data.

Results

qRT-PCR and Western blotting revealed a different expression pattern of ALDH1A1 in different malignant and non-malignant pancreatic cell lines. Immunohistochemical analysis demonstrated that ALDH1A1 was confined to the cellular cytoplasm and occurred in 72 cases (74%), whereas it was negative in 25 cases (26%). High expression of ALDH1A1 was significantly correlated to an increased proliferation rate (Spearman correlation, p = 0.01). Univariate and multivariate analyses showed that decreased expression of ALDH1A1 is an independent adverse prognostic factor for overall survival.

Conclusions

Immunonhistochemical analysis on whole-mount tissue slides revealed that ALDH1A1 is more abundantly expressed in pancreatic cancer than initially reported by a tissue microarray analysis. Moreover, high expression of ALDH1A1 correlated significantly with the proliferation of tumour cells. Intriguingly, this study is the first which identifies low expression of ALDH1A1 as an independent adverse prognostic marker for overall survival in pancreatic cancer.

Keywords:
Pancreatic cancer; ALDH1A1; prognostic marker; proliferation rate