Abstract
Human epidermal growth factor receptor 2 (HER2) is composed of an extracellular domain (ECD), a lipophilic transmembrane region and an intracellular domain (ICD). The most commonly used method to determine the status of HER2 is immunohistochemistry. However, false‑negative results are sometimes given, which causes some patients to lose the opportunity for anti‑HER2 therapy. We found that calpain‑10 may prohibit HER2‑ECD into peripheral blood resulting in a HER2‑negative result by the immunohistochemical method. We enrolled 289 patients into our experiment to assess the relationship between sHER2‑ECD and calpain‑10. The results showed that there was a positive correlation between sHER2‑ECD and calpain‑10. Moreover, we also investigated the prognostic values of sHER2‑ECD and calpain‑10 in breast cancer patients. According to the follow‑up results, positive sHER2‑ECD and tissue calpain‑10 were indicative of a poor prognosis in breast cancer patients. Subsequently, we further validated the relationship between the two molecules in in vitro experiments. In the in vitro experiments, the level of HER2‑ECD in the culture medium was increased or decreased with a decrease or increase in calpain‑10 by transfection technology, showing an inverse association. The results indicated that sHER2‑ECD and tissue calpain‑10 levels were powerful factors to assess the status of HER2. In combination with tissue HER2 detection, the occurrence of false‑negative HER2 was reduced, providing patients with additional treatment opportunities. In conclusion, sHER2‑ECD and tissue calpain‑10 may be used as new prognostic indices for breast cancer.