Inverse expression of caveolin-1 and EGFR in thyroid cancer patients.
Cytological analysis of fine-needle aspiration (FNA) is the first step in evaluation of patients with nodular thyroid disease with the primary goal to exclude thyroid malignancy. Its improvement by combining cytology with molecular markers is still a matter of investigation. In this study, 2 molecular markers were used: caveolin-1 and epidermal growth factor receptor (EGFR), along with the well-established genetic marker BRAF V600E mutation. We set out to determine the expression signatures of EGFR and caveolin-1 in patients with thyroid malignancy as well as to determine their possible association with disease severity. In FNA biopsy samples (n=186), immunocytochemical expression of caveolin-1 and BRAF V600E mutation coincided with malignancy. The patients were sorted according to 3 parameters: final histopathological diagnosis, caveolin-1 expression, and BRAF V600E mutation status before measurement of EGFR mRNA expression. EGFR upregulation was detected in the group of patients with malignant diagnosis, no caveolin-1 expression, and wild-type BRAF. Spearman rank correlation yielded a statistically significant negative correlation of EGFR and caveolin-1. Double immunofluorescence confirmed colocalization and inverse expression of EGFR and caveolin-1. Our data demonstrated that EGFR overexpression is associated with malignancy but not with tumor aggressiveness. Furthermore, high-caveolin-1/low-EGFR cases were associated with an advanced pT status and had a greater degree of neoplastic infiltration than low-caveolin-1/high-EGFR cases. Combining caveolin-1 and BRAF V600E with EGFR might help in recognizing more aggressive thyroid lesions in a pool of relatively indolent tumors in FNA biopsies and thus be useful for early risk stratification of thyroid cancer patients.
Institute for the Application of Nuclear Energy-INEP, Department for Endocrinology and Radioimmunology, University of Belgrade, 11080 Belgrade, Serbia.
Jelena
J
Janković
Institute of Pathology, Medical Faculty, University of Belgrade, 11000 Belgrade, Serbia.
Svetislav
S
Tatić
Clinical Center of Serbia, Department of Endocrine and Cardiovascular Pathology, 11000 Belgrade, Serbia.
Vesna
V
Božić
Center for Endocrine Surgery, Institute of Endocrinology, Diabetes and Diseases of Metabolism, University of Belgrade, 11000 Belgrade, Serbia.
Vladan
V
Živaljević
Institute for the Application of Nuclear Energy-INEP, Department for Endocrinology and Radioimmunology, University of Belgrade, 11080 Belgrade, Serbia.
Dubravka
D
Cvejić
Institute for the Application of Nuclear Energy-INEP, Department for Endocrinology and Radioimmunology, University of Belgrade, 11080 Belgrade, Serbia. Electronic address: svetlanap@inep.co.rs.
Svetlana
S
Paskaš
D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics*; D044963:Biopsy, Fine-Needle; D051242:Caveolin 1 / Q000032:analysis*; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000032:analysis / Q000235:genetics*; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation; D009367:Neoplasm Staging; D010641:Phenotype; D011237:Predictive Value of Tests; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000737:chemistry* / Q000235:genetics* / Q000473:pathology
D014408:Biomarkers, Tumor; C495540:CAV1 protein, human; D051242:Caveolin 1; C410723:epidermal growth factor receptor VIII; C512478:EGFR protein, human; D066246:ErbB Receptors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
BRAF V600E; Caveolin-1; EGFR; FNAB; Thyroid cancer