Coexistence of BRAFV600E mutation and EGFR overexpression is highly associated with adverse clinicopathological features of papillary thyroid carcinoma

Authors

  • Ivan Paunović 1. Center for Endocrine Surgery, Clinical Center of Serbia, Dr Koste Todorovića 8, Belgrade: 2. Faculty of Medicine, University of Belgrade, Dr Subotića Starijeg 6, Belgrade
  • Sonja Šelemetjev Department for Endocrinology and Radioimmunology, Institute for the Application of Nuclear Energy-INEP, University of Belgrade, Banatska 31b, Belgrade
  • Tijana Išić Denčić Department for Endocrinology and Radioimmunology, Institute for the Application of Nuclear Energy-INEP, University of Belgrade, Banatska 31b, Belgrade
  • Ilona Đorić Department for Endocrinology and Radioimmunology, Institute for the Application of Nuclear Energy-INEP, University of Belgrade, Banatska 31b, Belgrade
  • Jelena Janković Miljuš Department for Endocrinology and Radioimmunology, Institute for the Application of Nuclear Energy-INEP, University of Belgrade, Banatska 31b, Belgrade
  • Jelena Rončević Department for Endocrinology and Radioimmunology, Institute for the Application of Nuclear Energy-INEP, University of Belgrade, Banatska 31b, Belgrade
  • Dubravka Cvejić Department for Endocrinology and Radioimmunology, Institute for the Application of Nuclear Energy-INEP, University of Belgrade, Banatska 31b, Belgrade

Keywords:

epidermal growth factor receptor, BRAF V600E mutation, papillary thyroid carcinoma, predictive biomarkers, tumor progression

Abstract

Paper description:

  • Papillary thyroid carcinoma (PTC), usually curable, sometimes progresses to aggressive forms. Analysis of molecular alterations is helpful in predicting disease course and therapy decisions. BRAF gene mutations and epidermal growth factor receptor (EGFR) overexpression are associated with advanced stages of malignancy in several human cancers.
  • We report that in PTC, when present as a single alteration, BRAFV600E mutation or EGFR overexpression both correlate with adverse clinical parameters and their simultaneous presence significantly enhances the frequency of lymph metastases and local tumor invasion.
  • The coexistence of BRAFV600E mutation and EGFR overexpression identifies high risk patients as candidates for more serious treatment.


Abstract: Papillary thyroid carcinoma (PTC) generally has a good prognosis, but in a subset of patients it progresses to aggressive forms. Analysis of molecular alterations in relation to clinical phenotype may help in risk stratification of patients by predicting tumor aggressiveness. We analyzed the expression profiles of epidermal growth factor receptor (EGFR) using immunohistochemistry and the presence of BRAF(V600E) mutation by mutant allele-specific PCR in PTC tissue samples (n=92) in relation to clinicopathological parameters. BRAFV600E was detected in 46.7% of patients and correlated with the presence of lymph node metastasis (LNM, p=0.035) and extrathyroid invasion (EI, p<0.0001). EGFR overexpression was detected in 52.2% of the patients and also correlated with LNM (p<0.0001) and EI (p=0.027). Among patients with a single alteration, the presence of BRAFV600E impacted EI, while EGFR overexpression alone had a greater impact on LNM. The strongest association with adverse features was found in PTC patients with coexisting BRAFV600E and EGFR overexpression (28.3%), among whom LNM and EI were evident in 73% and 69%, respectively (p<0.0001, for both). Thus, the coexistence of BRAFV600E mutation and EGFR overexpression identifies high-risk PTC patients, who should be considered for combined molecular therapy offering a better long-term therapeutic outcome.

https://doi.org/10.2298/ABS190920064P

Received: September 20, 2019; Revised: October 16, 2019; Accepted: October 17, 2019; Published online: October 30, 2019

How to cite this article: Paunović I, Šelemetjev S, Išić Denčić T, Đorić I, Janković Miljuš J, Rončević J, Cvejić D. Coexistence of BRAFV600E mutation and EGFR overexpression is highly associated with adverse clinicopathological features of papillary thyroid carcinoma. Arch Biol Sci. 2020;72(1):37-44.

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Published

2020-03-24

How to Cite

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Paunović I, Šelemetjev S, Išić Denčić T, Đorić I, Janković Miljuš J, Rončević J, Cvejić D. Coexistence of BRAFV600E mutation and EGFR overexpression is highly associated with adverse clinicopathological features of papillary thyroid carcinoma. Arch Biol Sci [Internet]. 2020Mar.24 [cited 2022Aug.19];72(1):37-44. Available from: https://www.serbiosoc.org.rs/arch/index.php/abs/article/view/4653

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