Predictive value of EGFR-PI3K-pAKT-mTOR-pS6 pathway in sinonasal squamous cell carcinomas
Acta Otorrinolaringol Esp (Engl Ed). 2019 Jan-Feb;70(1):16-24.
doi: 10.1016/j.otorri.2017.10.005.
Epub 2018 Mar 21.
[Article in
English,
Spanish]
Affiliations
- 1 Departamento de Otorrinolaringología, Instituto Universitario de Oncología del Principado de Asturias, Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias, CIBERONC, ISCIII, Oviedo (Asturias), España.
- 2 Departamento de Otorrinolaringología, Instituto Universitario de Oncología del Principado de Asturias, Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias, CIBERONC, ISCIII, Oviedo (Asturias), España. Electronic address: flopez_1981@yahoo.es.
Abstract
Background and objectives:
We have previously indicated that EGFR has a role in carcinogenesis in a subgroup of sinonasal squamous cell carcinomas (SNSCC). In addition, EGFR activates 2 of the most important intracellular signalling pathways: PI3K/pAKT/mTOR/pS6 and MAP pathway kinases. The objective of this study was to evaluate the involvement of the EGFR/PI3K/pAKT/mTOR/pS6 pathway and its relationship with clinical-pathological parameters and follow-up of sinonasal squamous cell carcinoma.
Material and methods:
The immunohistochemical expression of different components of the PI3K/AKT/mTOR/pS6 pathway and its relationship with various clinical-pathological parameters was studied in a series of 54 patients with SNSCC.
Results:
Loss of PTEN expression was observed in 33/54 cases (61%) and pAKT, mTOR and pS6 pre-expression was observed in 19/54 cases (35%), 8/54 cases (15%), and 47/54 cases (87%), respectively. Loss of PTEN expression was related to intracranial invasion and development of regional metastases (p=0.005). Overexpression of pS6 was associated with a decrease in survival (p=0.008), presence of local recurrences (p=0.055), and worsening of overall prognosis (p=0.007). No significant relationships were observed between pAKT and mTOR expression and the clinicopathological parameters studied.
Conclusions:
Alterations in the expression of EGFR/PI3K/pAKT/mTOR/pS6 pathway components are common in a subgroup of SNSCC. This study reveals that the absence of pS6 overexpression is associated with better clinical outcomes. Therefore, pS6 expression could be considered as an unfavourable prognostic marker.
Keywords:
AKT; Carcinomas epidermoides nasosinusales; EGFR; Immunohistochemistry; Inmunohistoquímica; PTEN; Sinonasal squamous cell carcinomas; mTOR; pS6.
Copyright © 2018. Publicado por Elsevier España, S.L.U.
MeSH terms
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Aged
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Aged, 80 and over
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Biomarkers, Tumor / analysis*
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Carcinoma, Squamous Cell / chemistry
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Carcinoma, Squamous Cell / metabolism*
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Carcinoma, Squamous Cell / mortality
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ErbB Receptors / physiology
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Female
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Humans
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Lymphatic Metastasis
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Male
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Middle Aged
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Neoplasm Metastasis
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Neoplasm Proteins / analysis
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Neoplasm Proteins / genetics
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Neoplasm Proteins / physiology*
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Neoplasm Recurrence, Local
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Neoplasm Staging
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Nose Neoplasms / chemistry
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Nose Neoplasms / metabolism*
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Nose Neoplasms / mortality
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PTEN Phosphohydrolase / deficiency
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PTEN Phosphohydrolase / genetics
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PTEN Phosphohydrolase / physiology
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Paranasal Sinus Neoplasms / chemistry
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Paranasal Sinus Neoplasms / metabolism*
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Paranasal Sinus Neoplasms / mortality
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Phosphatidylinositol 3-Kinases / physiology
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Prognosis
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Proto-Oncogene Proteins c-akt / physiology
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Ribosomal Protein S6 Kinases / physiology
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Sequence Deletion
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Signal Transduction*
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TOR Serine-Threonine Kinases / physiology
Substances
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Biomarkers, Tumor
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Neoplasm Proteins
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MTOR protein, human
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EGFR protein, human
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ErbB Receptors
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AKT1 protein, human
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Proto-Oncogene Proteins c-akt
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Ribosomal Protein S6 Kinases
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TOR Serine-Threonine Kinases
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PTEN Phosphohydrolase
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PTEN protein, human