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


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).


CONCLUSIONS
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.
Division of Oncology, Second Department of Internal Medicine, Attikon University Hospital, Athens, Greece. Electronic address: dpsyrri@med.uoa.gr.
Amanda
A
Psyrri
Department 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.
Vassiliki
V
Kotoula
Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece.
Elena
E
Fountzilas
Health Data Specialists Ltd., Athens, Greece.
Zoi
Z
Alexopoulou
Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece.
Mattheos
M
Bobos
Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece.
Despina
D
Televantou
Department of Pathology, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece.
Georgia
G
Karayannopoulou
Department of Medical Oncology, "Papageorgiou" Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece.
Dimitrios
D
Krikelis
First Department of Otorhinolaryngology, "AHEPA" Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece.
Konstantinos
K
Markou
ENT Department, "G. Papanikolaou" General Hospital, Thessaloniki, Greece.
Ilias
I
Karasmanis
First Department of Otorhinolaryngology, "AHEPA" Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki, Greece.
Nikolaos
N
Angouridakis
Department 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.
Konstantine T
KT
Kalogeras
ENT Department, "G. Papanikolaou" General Hospital, Thessaloniki, Greece.
Angelos
A
Nikolaou
Laboratory 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.
George
G
Fountzilas
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007822:Laryngeal Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D051153:Wnt Proteins / Q000378:metabolism*
D051153:Wnt Proteins
Epithelial to mesenchymal transition; Mesenchymal to epithelial transition; Squamous cell carcinoma of the larynx; Wnt signaling