Growth factor receptors expression in anaplastic thyroid carcinoma: potential markers for therapeutic stratification.
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 beta, 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 beta, 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.
Elliott
Danielle D
DD
Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Sherman
Steven I
SI
Busaidy
Naifa L
NL
Williams
Michelle D
MD
Santarpia
Libero
L
Clayman
Gary L
GL
El-Naggar
Adel K
AK
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002277:Carcinoma / Q000175:diagnosis* / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D015854:Up-Regulation
D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; D020797:Receptor, Platelet-Derived Growth Factor beta; D017978:Receptors, Growth Factor; C508053:ERBB2 protein, human