1026P - Expression profiling of 21 biomolecules in locally advanced nasopharyngeal carcinomas (LA-NPC) of caucasian patients treated with chemotherapy or ch...

Date 01 October 2012
Event ESMO Congress 2012
Session Poster presentation III
Topics Anticancer agents
Head and Neck Cancers
Pathology/Molecular Biology
Surgical oncology
Basic Scientific Principles
Therapy
Biological therapy
Radiation oncology
Presenter Mattheos Bobos
Authors M. Bobos1, D. Krikelis1, G. Karayannopoulou1, L. Resiga2, S. Chrysafi1, E. Samantas3, D. Andreopoulos1, V. Vasiliou1, E. Ciuleanu4, G. Fountzilas5
  • 1Data Office, Hellenic Cooperative Oncology Group (HECOG), Athens/GR
  • 2Pathology Department, Cancer Institute Ion Chiricuta, Cluj/RO
  • 3Hellenic Cooperative Oncology Group (HECOG), Athens/GR
  • 4Medical Oncology - Radiation Oncology, Cancer Institute Ion Chiricuta, Cluj/RO
  • 5Medical Oncology Clinic, Hellenic Cooperative Oncology Group (HECOG), Athens/GR

Abstract

Introduction

Since scarce data exist on the pathogenesis of NPC in Caucasian patients, we attempted to elucidate the responsible molecular pathways in this patient population.

Patients and methods

Formalin-Fixed Paraffin-Embedded tumor tissue samples from 107 patients, diagnosed with LA-NPC and treated with chemotherapy or CRT, were analyzed by immunohistochemistry (IHC) for the expression of the following proteins: E-cadherin, P-cadherin, Fascin-1, Cyclin D1, COX-2, EGFR, VEGFA, VEGFC, VEGFR-2, VEGFR-3, ERCC1, p53, p63, Ki67, MAPT, phospho-p44/42MAPK, PTEN, phospho-Akt, phospho-mTOR, and phospho-GSK3b. EBER status was assessed by in situ hybridization. The majority of cases were included in tissue microarray. All stains were performed and assessed centrally by two pathologists. The median follow-up time was 76.8 (42.3 – 99.2) months.

Results

Biomolecules expressed in >90% of cases were: p53, COX-2, P-cadherin, EBER, phospho-GSK3b, and Fascin-1. WHO II + III tumors were more frequently EBER & PTEN positive and VEGFA negative. Advanced age was significantly associated with positive phospho-GSK3b and ERCC1 expression, male gender with positive phospho-Akt and phospho-p44/42MAPK, and worse performance status (PS), 1 or 2, with negative Ki67, ERCC1, PTEN, and phospho-mTOR expression. Earlier TNM stage was closely associated with p63, MAPT, PTEN, and Cyclin D1 positivity. Univariate Cox regression analysis highlighted Cyclin D1 as a negative prognostic factor for Disease-Free Survival (DFS) (p = 0.034) and EBER as a positive one for Overall Survival (OS) (p = 0.048). In multivariate analysis, advanced age and stage, poor PS, and positive ERCC1 emerged as predictors of worse DFS and OS, as opposed to positive phospho-mTOR. Clustering analysis defined two protein-expression groups being predictive of better OS (p = 0.043).

Conclusion

Our study is the first to examine the activation and interaction of established biomolecules and signaling pathways in Caucasian NPC patients in an effort to reveal new therapeutic targets.

Disclosure

All authors have declared no conflicts of interest.