Trophoblast Cell Surface Antigen 2 (Trop-2) Protein is Highly Expressed in Salivary Gland Carcinomas and Represents a Potential Therapeutic Target

Abstract

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.

TROP2 Expression in Sebaceous and Sweat Gland Carcinoma

“…TROP2 has recently attracted attention as a potential target for anticancer therapy. It is involved in a variety of cell signaling pathways [40], and high TROP2 expression is associated with metastasis through its regulation of epithelial-to-mesenchymal transition and linked to the dismal prognosis of cancer [19,20,31,41]. Blockade of TROP2 using specific antibodies produced potential anticancer activities in head and neck squamous cell carcinoma [42] and pancreatic cancer [43].…”

Trop-2 Therapy in Metastatic Triple-Negative Breast Cancer in Italy: Clinical Opportunity and Regulatory Pitfalls

“…Despite the several limitations of this study, such as inconsistency in Trop-2 detection and criteria of Trop-2 positivity, the authors stated that a frequent Trop-2 expression in the majority of solid tumors and its association with a poor prognosis provided a good rationale to target Trop-2 for therapeutic purposes [18]. Trop-2 expression has also been described in some rare and aggressive malignancies, such as salivary duct carcinomas [19], anaplastic thyroid carcinomas [20], uterine/ovarian carcinosarcomas [21,22], and neuroendocrine carcinoma (NEC) of the prostate [23]. In prostate (NEC), Trop-2 seems to closely interplay with the Poly ADP-ribose polymerase enzyme promoting neuroendocrine phenotype and aggressiveness of prostate cancer [24].…”

Trop2 Expression in Extramammary Paget’s Disease and Normal Skin

“…Trop2, encoded by the Tacstd2 gene, is a surface glycoprotein originally identified in human placental trophoblasts [16,17]. It is involved in a variety of cell signaling pathways, including proliferation, survival, self-renewal, and invasion [37]. Trop2 contains a hydrophobic transmembrane domain (extracellular domain) and an intracellular domain, and it is cleaved into the two parts via regulated intramembrane proteolysis [38].…”