Overxpression of HER2/neu in uterine carcinosarcoma

Abstract

Background: Uterine carcinosarcoma (UCS) is a rare tumor in gynecologic malignancy comprising less than 5% of uterine cancers, and is known to be clinically highly aggressive. UCS is often excluded from the eligibility of clinical trials, because of its rarity and poor prognosis. For recurrent or metastatic UCS, combination therapy of ifosfamide and paclitaxel is recommended as first line chemotherapy, and combination therapy of carboplatin and paclitaxel is also useful. However, the efficacy of existing chemotherapy for UCS is relatively limited and the research of molecular targeted therapy for UCS is behind in development because of its property. The main aim of this study is to evaluate HER2/neu expression status in UCS. Methods: After approval by the internal review board, we retrospectively evaluate HER2/ neu expression status in UCS, using the archives with formalin-fixed paraffin-embedded tissue blocks of UCS from patients. All patients were treated in National Cancer Center Hospital, Tokyo, Japan from 1998 to 2016, and the expression of HER2/neu in UCS was examined by immunohistochemistry (IHC), using polyclonal rabbit anti-HER2/neu antibody (A0485, DAKO, Carpinteria, CA). The expression of HER2/neu was scored as negative (0, 1+), equivocal (2+), positive (3+) in accordance with ASCO/CAP clinical practice guideline of breast cancer. Furthermore, carcinoma component (CC) and sarcoma component (SC) of the tumor were evaluated separately for its expression intensity. Results: Eighty-four cases were evaluated as UCS and 47 cases (56%) were negative/0, 1 + , 18 cases (21%) were equivocal/2 + , and 19 cases (23%) were positive/3+ in IHC. About the difference of HER2/neu expression between in CC and in SC, 37 cases (44%) stained 2 + /3+ over 10% in CC, whereas 0 cases (0%) stained 3+ and 8 cases (9.5%) stained 1 + /2+ over 10% in SC. HER2/neu in CC was significantly more expressed than in SC (p < 0.01). Conclusions: HER2/neu expression was identified in half of patients with UCS, and we must verify the significance of HER2 2+ in UCS by in situ hybridization (ISH). The current results suggest that molecular therapy targeted HER2 has a potential to be a new treatment for UCS.