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

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.

OR31-03 Single-Cell Profiling of Adult Human Ovarian Cortex Reveals Six Main Cell Types but No Germline Stem Cells

The human ovary orchestrates sex hormone production and undergoes monthly structural changes to release mature oocytes. The outer lining of the ovary (cortex) has a key role in defining fertility in women as it harbors the ovarian reserve. It has been suggested that oogonial stem cells exist in the ovarian cortex and that these can be captured by DDX4 antibody isolation. Our study aimed at comprehensive characterization of all cell types present in the ovarian cortex, including the previously reported oogonial stem cells. We developed methods to dissociate human ovarian cortex to a viable single cell solution allowing subsequent analysis by single cell transcriptomic profiling and cell surface antigen screening. In all analyses, cells captured by DDX4 antibodies (DDX4 Ab+) were included as a reference. High quality ovarian cortex tissue from gender reassignement and caesarean section patients was used in the analyses. Our single cell transcriptomic analyses based on >24,000 cells revealed the presence of six main cell types in ovarian cortex; oocytes, granulosa cells, immune cells, endothelial cells, perivascular cells, and stromal cells. Surface marker screening showed robust expression of 43 cell surface antigens in ovarian cortex cells. With the help of transcriptomic and cell surface antigen profiles, the DDX4 Ab+ cells were identified as perivascular cells. This finding was validated by immunostaining of ovarian tissue showing DDX4 Ab+ cells lining CD31 positive endothelial cells of blood vessels. To search for germline stem cells on a broader front, we compared our data with human fetal ovary cells including pre-meiotic germ cells (Li et al. 2017) and found no evidence for the presence of germ line stem cells of any kind in adult human ovarian cortex. In summary, we provide the first cell map of human ovarian cortex. Our results demonstrate six main cell types, but cannot provide support to the existence of oogonial stem cells. This dataset will be a valuable tool for studying the role of specific cell populations in ovarian biology, dissecting causes of infertility, and developing novel assisted reproductive technologies or even contraceptives.