970PD - Analysis of gene dosage aberrations of ErbB oncogene family in endometrial cancer

Date 30 September 2012
Event ESMO Congress 2012
Session Gynecological cancers
Topics Endometrial Cancer
Translational Research
Presenter Anna Supernat
Authors A.M. Supernat1, Z. Urban1, S. Lapinska-Szumczyk2, S. Sawicki2, D. Wydra2, A. Zaczek1
  • 1Department Of Medical Biotechnology, Medical University of Gdansk, 80-211 - Gdansk/PL
  • 2Department Of Gynaecology, Gynaecological Oncology And Gynaecological Endocrinology, Medical University of Gdansk, Gdansk/PL

Abstract

Introduction

ERBB (EGFR, epidermal growth factor receptor) family consists of four tyrosine kinase receptors: ERBB1, ERBB2, ERBB3 and ERBB4, which form a complex network of interacting signal transduction pathways. Excessive activation of the ERBB network, often found in tumors, is associated with rapid growth, proliferation, cell survival and also poor patient prognosis. Data about the importance of ERBB network in endometrial cancer is scarce. The purpose of this study was to determine the gene dosages of all the ERBB genes in endometrial cancer in the context of mutual dependence as well as clinicopathological parameters.

Materials and methods

The study group included 144 premenopausal and postmenopausal endometrial cancer patients, staged I-IV. Fresh frozen specimens, derived from primary tumors, were used as material for molecular analysis. Relative gene dosages of ERBB1, ERBB2, ERBB3 and ERBB4 were assessed by SYBR Green-based quantitative PCR, using ΔΔCt method.

Results

Gene dosages of individual ERBB genes correlated with each other. Particularly strong correlation occurred in case of ERBB2 and ERBB3 (p = 0.002), ERBB2 and ERBB4 (p <0.0000001,), ERBB3 and ERBB4 (p = 0.003) as well as ERBB1 and ERBB3 (p <0.0000001). Higher stage of the disease correlated with increased levels of ERBB2, ERBB3 and ERBB4 (p = 0.042, p = 0.0006, p = 0.005, respectively). The degree of lymph node involvement was associated with elevated levels of ERBB3 (p = 0.016) and ERBB4 (p = 0.024). The presence of metastases was associated with higher ERBB4 gene dosage (p = 0.0008), while high grade – with increased levels of ERBB1 (p = 0.007) and ERBB3 (p = 0.021).

Summary

Pattern of genetic aberrations of ERBB network varies depending on the stage of the disease. Deregulation of ERBB system is associated with more aggressive tumor characteristics and appears to be crucial in tumor progression.

Disclosure

All authors have declared no conflicts of interest.