Uterine carcinosarcoma (UCS), a rare and aggressive malignant neoplasm [1], is characterized by biphasic histology containing both carcinomatous and sarcomatous components. Based on immunohistochemical and molecular studies, the conversion theory has been proposed to explain UCS tumorigenesis [2], [3]. Extrauterine metastasis is common in UCS, with 61 % of patients initially presenting with the disease confined to the uterine corpus but later being diagnosed with occult metastases during comprehensive staging [4]. In addition, UCS has a high recurrence rate (40–60 %), with the majority of recurrences occurring within 1–2 years, and 5-year overall survival (OS) rates as low as 30 % [5]. The aggressiveness and poor prognosis of UCS necessitate the development of novel therapeutic targets.

Human epidermal growth factor receptor-2 (HER2) is a promising therapeutic target for UCS. Overexpression of HER2 protein (immunohistochemistry [IHC] score 3+) and gene amplification of HER2 reportedly range from 0 to 25 % [6], [7], [8], [9], [10] and 14 %–20 % of UCS cases [6], [10], [11], respectively. Additionally, recent results from a phase 2 clinical trial of trastuzumab deruxtecan, a novel HER2-targeting antibody drug conjugate (ADC) approved for the treatment of advanced HER2-positive breast and gastric cancer [12], [13], showed promising efficacy in patients with HER2-expressing UCS [14]. Interestingly, the HER2 ADC has a distinct pharmacological mode of action from trastuzumab [15], [16], [17]. Therefore, patients with low HER2 expression (HER2 score 1+) may benefit from ADC treatment [18]. Considering the different mode of action of HER2 ADC and its efficacy in HER2-low tumors, we would have to discriminate HER2 expressing UCS from HER2-null (IHC score 0) UCS for appropriate treatment selection in the near future.

Although HER2 expression in UCS has clinical significance for patients with metastatic or recurrent UCS who need systemic chemotherapy, little is known about changes in HER2 expression status between primary tumors and metastatic lesions. In some instances, the HER2 status between the primary tumor and metastases may differ. In approximately 10 % of breast cancer cases [19], [20] and 5 %–10 % of gastric cancer cases [21], [22], HER2 status changes between the primary and metastatic sites. Carcinosarcomas, on the other hand, are tumors with considerable intratumoral heterogeneity of HER2 expression [23], and larger discordance rates are anticipated; however, changes in HER2 expression between primary and metastatic sites have only been explored in a small number of cases to date [7], [9], [23].

This study aimed to clarify the HER2 expression status of metastatic lesions compared with that of the primary tumor in UCS. These results will shed light on the specimen type that should be used for HER2 testing to assess the indication for anti-HER2 therapy.