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Oral Oncol. 2014 Apr;50(4):298-305. doi: 10.1016/j.oraloncology.2014.01.005. Epub 2014 Jan 21.

Prognostic significance of the Wnt pathway in squamous cell laryngeal cancer.

Author information

  • 1Division of Oncology, Second Department of Internal Medicine, Attikon University Hospital, Athens, Greece. Electronic address: dpsyrri@med.uoa.gr.
  • 2Department of Pathology, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece; Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece.
  • 3Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece.
  • 4Health Data Specialists Ltd., Athens, Greece.
  • 5Department of Pathology, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece.
  • 6Department of Medical Oncology, "Papageorgiou" Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece.
  • 7First Department of Otorhinolaryngology, "AHEPA" Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece.
  • 8ENT Department, "G. Papanikolaou" General Hospital, Thessaloniki, Greece.
  • 9Department of Medical Oncology, "Papageorgiou" Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece; Translational Research Section, Hellenic Cooperative Oncology Group, Data Office, Athens, Greece.
  • 10Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece; Department of Medical Oncology, "Papageorgiou" Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece.

Abstract

OBJECTIVES:

We sought to determine the prognostic significance of the Wnt signaling pathway in operable squamous cell carcinoma of the larynx.

MATERIALS AND METHODS:

In an annotated cohort of 289 operable laryngeal cancers we evaluated the prognostic impact of E-cadherin, P-cadherin and β-catenin protein expression with immunohistochemistry, as well as the mRNA expression of 7 key effectors of the Wnt pathway including secreted frizzled-related protein 4 (SFRP4), SNAI2 (SLUG) and WNT5A with qPCR (relative quantification [RQ]).

RESULTS:

Using median immunoreactive scores as a pre-defined cut-off, patients whose tumors overexpressed both cytoplasmic E-cadherin and β-catenin experienced longer median OS as compared to those whose tumors overexpressed β-catenin only (median OS 124 vs. 72 months, p=0.0301) and patients whose tumors overexpressed both cytoplasmic and membranous E-cadherin experienced longer DFS as compared to those whose tumors overexpressed cytoplasmic E-cadherin only (median 118 vs. 91 months, p=0.0106). Upon hierarchical clustering of SFRP4, SNAI2 and WNT5A RQ values, profiles including co-expression of all 3 genes but also profiles with under-expression of SNAI2 and WNT5A were associated with worse outcome as compared to profiles not related to the Wnt pathway. In multivariate analysis, clustering was an independent predictor for DFS (p=0.0221) and OS (p=0.0077).

CONCLUSION:

We identified gene expression profiles and IHC patterns associated with aberrant Wnt signaling conferring aggressive clinical behavior in operable squamous cell carcinoma of the larynx. Prospective validation of these results will determine whether targeting the Wnt pathway merits investigation in this disease.

Copyright © 2014 Elsevier Ltd. All rights reserved.

KEYWORDS:

Epithelial to mesenchymal transition; Mesenchymal to epithelial transition; Squamous cell carcinoma of the larynx; Wnt signaling

PMID:
24461629
[PubMed - indexed for MEDLINE]
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