Aldehyde dehydrogenase 1 (ALDH1) has been suggested as a surrogate biomarker for cancer
stem cells in breast cancer and other tumors. We quantitatively measured ALDH1 in
two large cohorts of patients with non-small cell lung cancer (NSCLC) and investigated
its prognostic value. The AQUA method of quantitative immunofluorescence was used
to measure ALDH1 in 134 patients with NSCLC from Yale University and 296 patients
with NSCLC from Sotiria and Patras University hospitals in Greece, using tissue microarrays.
Patients were classified as positive or negative for ALDH1 based on the detection
threshold for quantitative immunofluorescence. Patients with squamous cell carcinoma
had higher scores than patients with adenocarcinoma. Detectable ALDH1 predicted better
prognosis in both cohorts (P = 0.0035 for the Yale cohort; P = 0.0238 for the Sotiria/Patras cohorts). The effect of ALDH1 expression was independent
of clinicopathologic factors in the Yale cohort (risk ratio = 3.2, P = 0.0008), but did not reach significance in the Sotiria/Patras cohort (hazard ratio
= 1.51, P = 0.08). Among patients with adenocarcinoma, the ALDH1-negative group had shorter
survival compared with the ALDH1-positive group in the Yale cohort (P = 0.00001), but not in the Sotiria/Patras cohort (P = 0.45). Unlike breast cancer, in which ALDH1 expression predicts poor outcome, in
NSCLC our exploratory and retrospective study indicates that ALDH1 expression is associated
with favorable outcome.
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References
- Global cancer statistics [Erratum appeared in CA Cancer J Clin 2011, 61:134].CA Cancer J Clin. 2011; 61: 69-90
- Gender, histology, and time of diagnosis are important factors for prognosis: analysis of 1499 never-smokers with advanced non-small cell lung cancer in Japan.J Thorac Oncol. 2010; 5: 1011-1017
- Prognostic factors for survival of stage I nonsmall cell lung cancer patients: a population-based analysis of 19,702 stage I patients in the California Cancer Registry from 1989 to 2003.Cancer. 2007; 110: 1532-1541
- Survival differences by gender for resected non-small cell lung cancer: a retrospective analysis of 12,509 cases in a Japanese Lung Cancer Registry study.J Thorac Oncol. 2010; 5: 1594-1601
- The impact of additional prognostic factors on survival and their relationship with the anatomical extent of disease expressed by the 6th edition of the TNM Classification of Malignant Tumors and the proposals for the 7th Edition.J Thorac Oncol. 2008; 3: 457-466
- Never-smoking nonsmall cell lung cancer as a separate entity: clinicopathologic features and survival.Cancer. 2008; 113: 1012-1018
- Analysis and update of the human aldehyde dehydrogenase (ALDH) gene family.Hum Genomics. 2005; 2: 138-143
- Human aldehyde dehydrogenase gene family.Eur J Biochem. 1998; 251: 549-557
- Functional characterization of highly purified human hematopoietic repopulating cells isolated according to aldehyde dehydrogenase activity.Blood. 2004; 104: 1648-1655
- ALDH1 as a functional marker of cancer stem and progenitor cells.Stem Cells Dev. 2009; 18: 17-25
- ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome.Cell Stem Cell. 2007; 1: 555-567
- Aldehyde dehydrogenase 1-positive cancer stem cells mediate metastasis and poor clinical outcome in inflammatory breast cancer.Clin Cancer Res. 2010; 16: 45-55
- Is ALDH1 a good method for definition of breast cancer stem cells?.Breast Cancer Res Treat. 2010; 123: 109-111
- In situ identification of putative cancer stem cells by multiplexing ALDH1, CD44, and cytokeratin identifies breast cancer patients with poor prognosis.Am J Pathol. 2010; 176: 2131-2138
- 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: 4234-4241
- Aldehyde dehydrogenase activity of breast cancer stem cells is primarily due to isoform ALDH1A3 and its expression is predictive of metastasis.Stem Cells. 2011; 29: 32-45
- Finding cancer stem cells: are aldehyde dehydrogenases fit for purpose?.J Pathol. 2010; 222: 335-344
- Analytic variability in immunohistochemistry biomarker studies.Cancer Epidemiol Biomarkers Prev. 2010; 19: 982-991
- The new World Health Organization classification of lung tumours.Eur Respir J. 2001; 18: 1059-1068
- The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM.Ann Surg Oncol. 2010; 17: 1471-1474
- Automated quantitative analysis (AQUA) of in situ protein expression, antibody concentration, and prognosis.J Natl Cancer Inst. 2005; 97: 1808-1815
- Automated subcellular localization and quantification of protein expression in tissue microarrays.Nat Med. 2002; 8: 1323-1327
- Automated analysis of tissue microarrays.Methods Mol Biol. 2010; 664: 151-162
- Epithelial mesenchymal transition and hedgehog signaling activation are associated with chemoresistance and invasion of hepatoma subpopulations.J Hepatol. 2011; 55: 838-845
- Distinct expression levels and patterns of stem cell marker, aldehyde dehydrogenase isoform 1 (ALDH1), in human epithelial cancers.PLoS One. 2010; 5: e10277
- Differential expression of aldehyde dehydrogenase 1a1 (ALDH1) in normal ovary and serous ovarian tumors.J Ovarian Res. 2010; 3: 28
- ALDH1 expression correlates with favorable prognosis in ovarian cancers.Mod Pathol. 2009; 22: 817-823
- Aldehyde dehydrogenase 1 is a tumor stem cell-associated marker in lung cancer.Mol Cancer Res. 2009; 7: 330-338
- Aldehyde dehydrogenase activity selects for lung adenocarcinoma stem cells dependent on notch signaling.Cancer Res. 2010; 70: 9937-9948
- ALDH1A1 and ALDH3A1 expression in lung cancers: correlation with histologic type and potential precursors.Lung Cancer. 2008; 59: 340-349
- Aldehyde dehydrogenase-1 is a specific marker for stem cells in human lung adenocarcinoma.Med Oncol. 2012; 29: 633-639
Article info
Publication history
Published online: August 08, 2012
Accepted:
June 20,
2012
Footnotes
Supported in part by the Oncology Unit of the Sotiria General Hospital, Athens, Greece, and Department of Public Health Grant #2009-0097 from the State of Connecticut (D.L.R.).
D.L.R. declares a duality of interest as a cofounder, consultant, and stockholder of HistoRx. This company was founded by Yale University and is the exclusive Yale licensee of the AQUA technology developed in the laboratory of D.L.R. AQUA is a registered trademark of HistoRx.
Supplemental material for this article can be found at http://ajp.amjpathol.org or at http://dx.doi.org/10.1016/j.ajpath.2012.06.037.
Current address A.D.: Department of Internal Medicine, Albert Einstein Medical Center, Philadelphia, Pennsylvania.
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© 2012 American Society for Investigative Pathology. Published by Elsevier Inc.
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