1185P - Prognostic role of ErbB family receptors, Myc and mitogen-activated protein kinase (MAPK) in patients with early-stage non small-cell lung cancer

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Non-Small-Cell Lung Cancer, Early Stage
Translational Research
Presenter Vienna Ludovini
Authors V. Ludovini1, G. Bellezza2, F. Bianconi3, R. Chiari1, C. Bennati1, F.R. Tofanetti1, J. Vannucci4, F. Puma4, A. Sidoni2, L. Crinò5
  • 1Medical Oncology Division, S. Maria della Misericordia Hospital,, 06132 - Perugia/IT
  • 2University Of Perugia, Institute of Pathological Anatomy and Histology, University of Perugia, Perugia, Italy, 06132 - Perugia/IT
  • 3University of Perugia, 06036 - Perugia/IT
  • 4Department Of Thoracic Surgery,, University of Perugia,, Perugia/IT
  • 5Oncologia Medica, S. Maria della Misericordia Hospital,, 06132 - Perugia/IT

Abstract

Background

EGFR deregulation has been extensively studied in non small-cell lung cancer (NSCLC), but the expression and the role of other ErbB receptors and their downstream signal transductions remains still unclear. MYC and MAPK are key downstream components of the EGFR pathway and have significant roles in cell survival, proliferation, and growth. This study evaluates the prognostic role of EGFR, ErbB2, ErbB3, ErbB4, MYC and MAPK by immunohistochemistry (IHC) in early stage NSCLC.

Methods

One-hundred nine NSCLC patients were evaluated: median age was 67 years (range 40–84); Male/Female: 93/16; squamous (SCC)/adenocarcinoma (ADC)/BAC/other: 52/36/3/18; smoker/never smoker:100/9, and stage I/II/III:67/17/25. IHC results were evaluated by two independent observers and the tumors with ≥10% positive cells were classified positive, further confirmed by Receiver Operating Characteristic (ROC) analysis. Kaplan-Meier estimates of survival and time to recurrence were calculated for clinical and biologic variables using Cox model for multivariate analysis.

Results

EGFR was expressed in 55.9%, ErbB2 in 24.7% ErbB3 in 33.9%, ErbB4 in 27.5%, Myc in 23.8% and MAPK in 27.5 % of patients, respectively. EGFR and ErbB3 were associated with SCC (p < 0.0001 and p = 0.004, respectively) whereas ErbB2 and MYC with ADC (p = 0.004 and p < 0.0001, respectively). EGFR and ErbB3 were significantly associated (p = 0.003), as well as MAPK and ErbB4 (p = 0.02). At a median follow-up of 75 months the contemporary over-expression of EGFR, ErbB2 and MAPK was associated with shorter disease free survival (DFS) (HR = 5.4, p = 0.002) and overall survival (OS) (HR = 8.9, p < 0.0001). At multivariate analysis adjusting for stage, the co-expression of EGFR, ErbB2 and MAPK was an independent predictor for worse DFS and OS (HR = 5.7, p = 0.004; HR = 8.67, p < 0.001, respectively).

Conclusions

Our results suggest that in early stage NSCLC the co-expression of EGFR, ErbB2 and MAPK predicted a worse prognosis. Such features may have important implications for future targeted therapies. We thank Italian Association for Cancer Research (AIRC) for supporting the study.

Disclosure

All authors have declared no conflicts of interest.