TY - JOUR
T1 - Growth factor receptors expression in anaplastic thyroid carcinoma
T2 - potential markers for therapeutic stratification
AU - Elliott, Danielle D.
AU - Sherman, Steven I.
AU - Busaidy, Naifa L.
AU - Williams, Michelle D.
AU - Santarpia, Libero
AU - Clayman, Gary L.
AU - El-Naggar, Adel K.
N1 - Funding Information:
This study was supported in part by the Kenneth D. Müller Professorship, National Cancer Institute Specialized Program of Research Excellence Grant in Head and Neck Cancer (SPORE) (AEN), and the National Cancer Institute Grant CA-16672.
PY - 2008/1
Y1 - 2008/1
N2 - Anaplastic thyroid carcinoma is a rare and universally fatal disease. Therefore, novel biomarkers are needed as surrogate end points in triaging patients for novel and selective biologic treatments. Up-regulation of several growth factor receptors has been shown to be associated with the biologic progression and response to targeted therapy of several malignancies. To determine the role of growth factor receptors in the biologic stratification of anaplastic thyroid carcinoma, we studied the expression of epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor β, and HER-2 receptor in a large cohort of anaplastic thyroid carcinomas by immunohistochemical techniques. The percentage of positive cells, staining intensity and localization of staining in the anaplastic component, and coexisting well-differentiated thyroid carcinoma and adjacent nonneoplastic thyroid were evaluated for these markers. EGFR, platelet-derived growth factor receptor β, and HER-2 were overexpressed in 58%, 16%, and 16% of anaplastic carcinomas, respectively. In tumors with adjacent normal thyroid parenchyma and/or differentiated carcinoma components, overexpression of all 3 markers was noted exclusively in the anaplastic component. Mutational analysis of exons 18, 19, and 21 of the EGFR gene showed no mutations in all anaplastic carcinomas. We conclude that the expression of these markers (1) may play a role in a subset of thyroid tumorigenesis and anaplastic transformation and (2) can be validated for potential use in the stratification of patients for targeted therapy.
AB - Anaplastic thyroid carcinoma is a rare and universally fatal disease. Therefore, novel biomarkers are needed as surrogate end points in triaging patients for novel and selective biologic treatments. Up-regulation of several growth factor receptors has been shown to be associated with the biologic progression and response to targeted therapy of several malignancies. To determine the role of growth factor receptors in the biologic stratification of anaplastic thyroid carcinoma, we studied the expression of epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor β, and HER-2 receptor in a large cohort of anaplastic thyroid carcinomas by immunohistochemical techniques. The percentage of positive cells, staining intensity and localization of staining in the anaplastic component, and coexisting well-differentiated thyroid carcinoma and adjacent nonneoplastic thyroid were evaluated for these markers. EGFR, platelet-derived growth factor receptor β, and HER-2 were overexpressed in 58%, 16%, and 16% of anaplastic carcinomas, respectively. In tumors with adjacent normal thyroid parenchyma and/or differentiated carcinoma components, overexpression of all 3 markers was noted exclusively in the anaplastic component. Mutational analysis of exons 18, 19, and 21 of the EGFR gene showed no mutations in all anaplastic carcinomas. We conclude that the expression of these markers (1) may play a role in a subset of thyroid tumorigenesis and anaplastic transformation and (2) can be validated for potential use in the stratification of patients for targeted therapy.
KW - Anaplastic thyroid carcinoma
KW - EGFR
KW - Growth factors
KW - HER-2
KW - PDGFR
KW - Targeted therapy
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U2 - 10.1016/j.humpath.2007.05.012
DO - 10.1016/j.humpath.2007.05.012
M3 - Article
C2 - 17949783
AN - SCOPUS:36748999952
SN - 0046-8177
VL - 39
SP - 15
EP - 20
JO - Human Pathology
JF - Human Pathology
IS - 1
ER -