@article{3156941,
    title = "Cyclin D1, EGFR, and Akt/mTOR pathway",
    author = "Dionysopoulos, D. and Pavlakis, K. and Kotoula, V. and Fountzilas, E. and and Markou, K. and Karasmanis, I. and Angouridakis, N. and Nikolaou, A. and and Kalogeras, K. T. and Fountzilas, G.",
    journal = "Strahlentherapie und Onkologie",
    year = "2013",
    volume = "189",
    number = "3",
    pages = "202-214",
    publisher = "Springer Berlin Heidelberg",
    issn = "0179-7158, 1439-099X",
    doi = "10.1007/s00066-012-0275-0",
    keywords = "Epidermal growth factor receptor; Akt; mTOR; Prognostic factors;
Laryngeal neoplasms",
    abstract = "EGFR (epidermal growth factor receptor), cyclin D1 and Akt/mTOR pathways
are active in head and neck cancer. The aim of this study was to explore
biomarker expression, their correlations with clinicopathological
parameters and their prognostic utility in a cohort of patients with
localized squamous laryngeal carcinoma.
We assessed relative messenger RNA expression of EGFR, Akt1, 2, and 3,
mTOR and CCND1, copy number variants of the EGFR and CCND1 genes and
immunohistochemical protein expression of EGFR, p-Akt308, p-Akt473,
pmTOR, PTEN, p53 and cyclin D1 in paraffin-embedded tissue samples of
localized laryngeal carcinomas.
In 289 patients with T3-4 (77.8%), node-negative (84.1%) tumors of the
larynx, high EGFR and CCND1 mRNA correlated with no or ex-smoking, (p =
0.003 and p = 0.029, respectively), while low Akt3 mRNA correlated with
alcohol abuse, N0 stage, total laryngectomy, and absence of neck
dissection. At a median follow-up of 74.5 months, high mTOR mRNA
expression was marginally associated with shorter disease-free survival
(hazard ratio [HR] = 1.54; p = 0.093) and high Akt3 mRNA with shorter
overall survival (HR = 1.49; p = 0.0786), in univariate analysis. In
multivariate analysis, node-positive status, subglottic-transglottic
location, surgery other than total laryngectomy and mTOR/CCND1 mRNA
interaction with a hazard ratio of 2.16 (p value for interaction:
0.0010) were independent predictors of relapse, while node-positive
status and subglottic-transglottic location were associated with higher
risk for death.
In localized laryngeal cancer, clinicopathological parameters and an
interaction of high mTOR and CCND1 mRNA expression were found to be
associated with poor patient outcome."
}