Trophoblast Cell Surface Antigen 2 (Trop-2) Protein is Highly Expressed in Salivary Gland Carcinomas and Represents a Potential Therapeutic Target.
Philipp WolberLisa NachtsheimFranziska HoffmannJens Peter KlußmannMoritz MeyerFerdinand von EggelingOrlando Guntinas-LichiusAlexander QuaasChristoph AroltPublished in: Head and neck pathology (2021)
Treatment options for unresectable, recurrent or metastatic salivary gland carcinomas (SGC) are scarce. Trophoblast cell surface antigen 2 (Trop-2) is a transmembrane glycoprotein that is involved in a variety of oncogenic cell signaling pathways. Its potential as a target for the antibody-drug conjugate sacituzumab govitecan has already been demonstrated in different tumor entities. The United States Food and Drug Administration approved this antibody-drug conjugate for the treatment of metastatic triple-negative breast cancer. Here, we aimed to investigate Trop-2 protein expression in different entities of SGCs. We retrospectively reviewed the medical records of all patients that underwent surgery for a primary SGC in a tertiary referral center between 1990 and 2014. Immunohistochemical (IHC) staining for Trop-2 was performed and rated as negative, weak, moderate or high using a semiquantitative score. Additionally, representative cases were analyzed using MALDI-mass spectrometry (MS) imaging to confirm the IHC results. The cohort consisted of 114 tumors of the parotid gland (90.4%) and submandibular gland (9.6%). It mainly included mucoepidermoid, salivary duct and adenoid cystic carcinomas. In IHC samples, 44% showed high, 38% moderate and 10% weak expression rates of Trop-2. MALDI-MS imaging confirmed the presence of Trop-2 protein in 80% of the tested tumor samples. This is the first study to demonstrate that several types of SGC express Trop-2 with variable intensity. Since there are currently few systemic treatment options for advanced SGCs, Trop-2 represents a promising target for further clinical studies, for instance, with sacituzumab govitecan.
Keyphrases
- mass spectrometry
- cell surface
- high resolution
- liquid chromatography
- drug administration
- end stage renal disease
- high grade
- small cell lung cancer
- squamous cell carcinoma
- high intensity
- chronic kidney disease
- healthcare
- ms ms
- multiple sclerosis
- binding protein
- ejection fraction
- primary care
- newly diagnosed
- gas chromatography
- capillary electrophoresis
- signaling pathway
- cell proliferation
- epithelial mesenchymal transition
- protein protein
- risk assessment
- stem cells
- cancer therapy
- coronary artery disease
- prognostic factors
- radiation therapy
- photodynamic therapy
- acute coronary syndrome
- cell therapy
- coronary artery bypass
- locally advanced
- percutaneous coronary intervention