Cyclin D1, EGFR, and Akt/mTOR pathway. Potential prognostic markers in localized laryngeal squamous cell carcinoma.

Abstract

INTRODUCTION:

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.

PATIENTS AND METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

• Authors: D Dionysopoulos, K Pavlakis, V Kotoula, E Fountzilas, K Markou, I Karasmanis, N Angouridakis, A Nikolaou, K T Kalogeras, G Fountzilas
• Journal: Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] (Strahlenther Onkol) Vol. 189 Issue 3 Pg. 202-14 (Mar 2013) ISSN: 1439-099X [Electronic] Germany
• PMID: 23400686 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• CCND1 protein, human
• RNA, Messenger
• Cyclin D1
• MTOR protein, human
• EGFR protein, human
• ErbB Receptors
• TOR Serine-Threonine Kinases

Topics

• Adult
• Aged
• Aged, 80 and over
• Biomarkers, Tumor (genetics)
• Carcinoma, Squamous Cell (genetics, pathology, radiotherapy, surgery)
• Combined Modality Therapy
• Cyclin D1 (genetics)
• ErbB Receptors (genetics)
• Female
• Humans
• Laryngeal Neoplasms (genetics, pathology, radiotherapy, surgery)
• Lymphatic Metastasis (genetics, pathology, radiotherapy)
• Male
• Middle Aged
• Neoplasm Staging
• Prognosis
• RNA, Messenger (genetics)
• Retrospective Studies
• TOR Serine-Threonine Kinases (genetics)