[589] Epidermal Growth Factor Receptor Over-Expression in Thyroid Neoplasia Associates with Chromosome 7 Polysomy

MD Williams, ME Cabanillas, GL Clayman. UT M.D. Anderson Cancer Center, Houston, TX

Background: Epidermal growth factor receptor (EGFR) activation is a prominent contributor to tumor proliferation and angiogenesis. Alterations in the EGFR gene including copy number changes have correlated with response to some tyrosine kinase inhibitors in other tumor types. Understanding mechanisms of EGFR activation in thyroid neoplasia may provide additional pathways for targeted therapy in advanced patients.
Design: Forty-nine thyroid tumors including 20 follicular carcinomas (FC),15 medullary carcinomas (MTC), 9 papillary carcinomas (PTC), and 5 anaplastic carcinomas(ATC) comprised a tissue microarray used for the following studies. EGFR expression was evaluated by immunohistochemistry (Clone 31G7, 1:50, Zymed) and scored 0-3+. The EGFR gene and Chromosome 7 copy number were assessed by fluorescence in situ hybridization (FISH); polysomy was defined as 3 or more copies in >=10% of cells.
Results: EGFR was over-expressed (3+) in 11 of 49 (22.4%) tumors (4/20 FC, 3/15 MTC, 1/9 PTC, 2/5 ATC). Ten of the 11 (90.9%) tumors with high EGFR expression also showed chromosome 7 polysomy (p=0.0002). Chromosome 7 polysomy was present in 20 of 49 (40.8%) tumors (8/20 FC, 7/15 MTC, 3/9 PTC, 2/5 ATC). High polysomy (>40% of cells with 3+ copies) was present in 9 of the 20 (45.0%) polysomic tumors. EGFR gene amplification was not identified.
Conclusions: EGFR is 1) over-expressed in a subset of thyroid neoplasms (follicular and c-cell origin), and correlates with chromosome 7 polysomy. 2) Polysomy was not limited to high EGFR expressing tumors. 3) As polysomy maybe a marker of response to targeted therapies, further evaluation of EGFR and polysomy by FISH in advanced thyroid patients is warranted.
Category: Endocrine

Tuesday, March 23, 2010 1:00 PM

Poster Session IV # 46, Tuesday Afternoon

 

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