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HER receptor and ligand protein overexpressed in patients with thymic carcinoma
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Epidermal growth factor receptor and HER-2 amplification is rare in thymic carcinoma, according to study results.
However, protein expression for HER receptors — and their ligands — was common, a finding that suggests these molecules could be potential treatment targets.
Previous studies have demonstrated that EGFR, phosphorylated EGFR (pEGFR), HER-2 and HER-3–positive tumors are commonly associated with a poor prognosis. However, as a predictive marker, measurement of EGFR by immunohistochemistry has been obstructive in identifying patients likely to respond to targeted therapy in cases of non–small cell lung cancer, head and neck cancers, or colorectal cancer.
For example, in NSCLC, only specific activating EGFR mutations are associated with response to targeted treatment with the tyrosine kinase inhibitors gefitinib (Iressa, AstraZeneca) or erlotinib (Tarceva, OSI Pharmaceuticals).
To determine the frequency of protein expression of the HER family of receptors and its ligands, as well as gene amplification for EGFR and HER-2, researchers utilized fluorescence in situ hybridization analysis in a series of thymic carcinoma to differentiate molecular changes that could potentially identify therapeutic targets for these tumors.
Researchers examined twenty-four cases of thymic squamous cell carcinoma — derived from thymectomy specimens from the surgical pathology files of The University of Texas MD Anderson Cancer Center — for immunohistochemical expression of EGFR, pEGFR, HER-2, phosphorylated HER-2, HER-3, phosphorylated HER-3 and their ligands epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), amphiregulin and epiregulin.
Whole histological sections from formalin-fixed, paraffin-embedded tumor tissue stained with hematoxylin and eosin, as well as corresponding unstained slides for immunohistochemistry and fluorescence in situ hybridization analyses, were available in all cases.
Significant immunohistochemical expression was observed for EGFR (33.3%), pEGFR (33.3%), HER-2 (58.3%), HER-3 (45.8%), TGF-alpha (54.1%), amphiregulin (25%) and epiregulin (91.7%), according to study results. One case showed HER-2 gene amplification by fluorescence in situ hybridization. Increased EGFR was found in two cases (8.4%), and increased HER-2 gene copy numbers were observed in 18 cases (75%). In addition, eight cases (33.3%) demonstrated an increased HER-2:CEP17 ratio.
“The findings of our study indicate that although amplification of EGFR and HER2 genes in thymic carcinoma is an uncommon occurrence, other molecular alterations — including increased EGFR and HER2 gene copy numbers, as well as HER receptor and ligand protein overexpression — do exist,” the researchers wrote. “Although to date, the results on treatment response to HER antagonists in the setting of protein overexpression alone are variable, exploration of these molecules as potential treatment targets in thymic carcinoma may still be warranted.”
In addition, the researchers cautioned that “although this study comprises a relatively large study of a rare neoplasm, the series may not be large enough to perform potent survival analysis. Further studies investigating a larger number of tumors are recommended to determine the exact underlying molecular events affecting HER receptors and ligands, thereby identifying possible new targets for the therapy of thymic carcinoma.”
Disclosure: The researchers report no relevant financial disclosures.
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