HER2 expression is exceedingly rare in anaplastic thyroid carcinoma: an immunohistochemical analysis of 50 surgical cases

Anaplastic thyroid carcinoma (ATC) is one of the most lethal human solid tumors and urgently requires novel therapeutic targets. The HER2/ERBB2 receptor tyrosine kinase is an established biomarker and drug target in breast and gastric cancers, but its relevance in ATC remains uncertain. We performed a retrospective, single‑centre immunohistochemical (IHC) study of 50 consecutive surgical ATC specimens. Formalin‑fixed paraffin‑embedded sections with sufficient viable tumour were stained on the BenchMark ULTRA platform (Ventana, USA) using the Her‑2/neu clone 4B5 rabbit monoclonal antibody. Membranous staining intensity and completeness were scored by two pathologists according to the College of American Pathologists (CAP) guideline for breast carcinoma. All 50 ATC cases were negative for HER2 overexpression. Three tumours showed only focal, granular, intracytoplasmic signal in tumour cells and macrophages; no case demonstrated a strong, complete (3+) membranous pattern. These data indicate that true HER2 protein overexpression is exceedingly rare in ATC. Our results do not support routine HER2 testing or anti‑HER2 monotherapy in unselected patients with ATC. Nevertheless, preclinical studies suggest that pan‑ERBB inhibition may cooperate with BRAF/MEK blockade to prevent pathway reactivation and overcome resistance in BRAFV600E‑mutant thyroid cancer. Prospective trials with molecular stratification are warranted.