1030P - Insulin growth factor receptor as a prognostic marker in operable squamous-cell laryngeal cancer

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Head and Neck Cancers
Translational Research
Presenter Giannis Mountzios
Authors G. Mountzios1, I. Kostopoulos2, V. Kotoula3, S. Levva4, E. Fountzilas4, K. Markou5, I. Karasmanis6, N. Angouridakis5, A. Nikolaou6, G. Fountzilas7
  • 1Medical Oncology, 251 Airforce General Hospital, 115 25 - Athens/GR
  • 2Pathology, Aristotle University of Thessalonikii School of Medicine, Thessaloniki/GR
  • 3Molecular Biology, Hellenic Foundation for Cancer Research, Thessaloniki/GR
  • 4Medical Oncology Clinic Aristotle University Of Thessaloniki, Papageorgiou General Hospital Aristotle University of Thessaloniki, 564 29 - Thessaloniki/GR
  • 5Department Of Otorhinolaryngology, AHEPA Hospital, Aristotle University of Thessaloniki School of Medicine, Thessaloniki/GR
  • 6Ent Department, "G. Papanikolaou" General Hospital, Thessaloniki/GR
  • 7Medical Oncology Clinic, Papageorgiou General Hospital Aristotle University of Thessaloniki, 564 29 - Thessaloniki/GR

Abstract

Introduction

Prognosis of patients with operable squamous-cell laryngeal cancer is highly variable and therefore potent prognostic biomarkers are warranted. The Insulin-Growth Factor Receptor (IGFR)-mediated signaling pathway plays a critical role in laryngeal carcinogenesis.

Patients and methods

We identified all patients with localised TNM stage I-III laryngeal cancer managed with potentially curative laryngectomy between May 1985 and June 2008. Immunohistochemical (ICH) expression of IGFR1-alpha, IGFR1-beta and IGFR2 was evaluated using the Histo-score (H-score) climax and mRNA levels of important effectors of the IGFR-mediated pathway were assessed, including IGFR1, IGF-binding protein 3 (IGFBP3), suppressor of cytokine signaling 2 (SOCS2) and members of the MAP-kinase (MA2K1, MAPK9) and phosphatidyl-inositol-3 kinase (PI3KCA, PI3KR1) families. Cox-regression models were applied to assess the predictive value of the components of the IGFR-mediated pathway on disease-free survival (DFS) and overall survival (OS).

Results

Among 289 eligible patients, 95.8% were male, 95.2% were current or ex smokers, 75.4% were alcohol abusers, 15.6% had node-positive diease and 32.2% had received post-operative irradiation. After a median follow-up of 74.5 months, median DFS was 94.5 months and median OS was 106.3 months. Using the median H-score as the pre-defined cut-off value, IGFR1-alpha overexpression was associated with decreased DFS (p = 0.0538) and OS (p = 0.0157). Increased mRNA levels of MAPK9 were associated with prolonged DFS (p = 0.0209) and OS (p = 0.0108), as were increased mRNA levels of PI3KCA, albeit not significantly (p = 0.0723 and 0.0726 for DFS and OS respectively). In multivariate analysis, IGFR1-alpha overexpression was associated with a 46.6% increase in the probability for relapse (p = 0.0374). Independent predictors for poor OS included node-positive disease (HR = 2.569, 95%CI: 1.610-4.100, p < 0.0001), subglotic or transglotic location (HR = 1.756, 95%CI: 1.016-3.036, p = 0.0438) and IGFR1-alpha IHC overexpression (HR = 1.475, 95%CI: 1.000-2.178, p = 0.05).

Conclusion

IGFR1-alpha IHC overexpression may serve as an independent predictor of relapse and survival in operable laryngeal cancer. Prospective evaluation of IGFR1-alpha prognostic utility is warranted.

Disclosure

All authors have declared no conflicts of interest.