Epidermal growth factor receptor 1 expression is upregulated in undifferentiated thyroid carcinomas in humans.
BACKGROUND
Epidermal growth factor receptor 1 (EGFR1) signaling is involved in human cancer cell progression and is responsible for aggressive biological behavior and poor clinical outcome in several human malignancies. Activation of the EGFR1 pathway has been proposed, among others, as being involved in the progression of thyroid cancer toward a thyroid-stimulating hormone (TSH)-independent phenotype. We have previously observed that undifferentiated thyroid carcinoma cells are hyper-sensitive to EGF signaling of downstream intracellular pathways, and this correlated both with the loss of TSH-dependency and increase in EGF-dependent proliferation and migration. Thus, we hypothesized that the upregulation of EGFR1 protein expression may be enhanced in parallel with transition toward a poorly differentiated phenotype in human thyroid carcinomas.


METHODS
The expression of EGFR1 was evaluated, by immunohistochemistry, in a series of 49 human thyroid carcinomas at different degrees of tumor differentiation.


RESULTS
The expression of EGFR1 protein was significantly upregulated in poorly differentiated and anaplastic thyroid carcinomas, whereas it was absent or faint in normal thyroid gland tissue and in differentiated thyroid papillary carcinomas. Of note, selected thyroid tumors characterized by a mixed population of differentiated and undifferentiated tumor cells, likely progressing from well to poorly differentiated and anaplastic phenotypes, exhibited EGFR1-negative differentiated fields together with EGFR1-positive poorly differentiated and anaplastic areas.


CONCLUSIONS
Upregulation of EGFR1 expression may be a molecular marker of dedifferentiation in thyroid epithelial carcinomas, likely being responsible for the activation of EGF signaling observed in tumor cells and favoring progression toward an angiogenic, poorly differentiated, TSH-independent phenotype.
Clinical Oncology Unit, University of Foggia, Foggia, Italy. m.landriscina@unifg.it
Matteo
M
Landriscina
Giuseppe
G
Pannone
Annamaria
A
Piscazzi
Paolo
P
Toti
Annarita
A
Fabiano
Simona
S
Tortorella
Rossella
R
Occhini
Antonio
A
Ambrosi
Pantaleo
P
Bufo
Mauro
M
Cignarelli
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D002277:Carcinoma; D002291:Carcinoma, Papillary; D054337:Cell Dedifferentiation; D018450:Disease Progression; D066246:ErbB Receptors / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000201:enzymology / Q000473:pathology*; D015854:Up-Regulation; D055815:Young Adult
D014408:Biomarkers, Tumor; C512478:EGFR protein, human; D066246:ErbB Receptors