The Role of Mesothelin Expression in Serous Ovarian Carcinoma: Impacts on Diagnosis, Prognosis, and Therapeutic Targets

SIMPLE SUMMARY: Ovarian cancer is the most lethal gynaecological malignancy, of which serous carcinoma is the most common subtype. The lack of symptoms and sensitive diagnostic tests for the early stages of its development may explain why diagnosis often occurs late, when the neoplasm has already spread outside the pelvis. Currently, the standard treatment for high-grade serous ovarian carcinomas (HSOCs) involves cytoreductive surgery followed by platinum-based systematic chemotherapy, which does not reduce either recurrence or mortality. Despite intense efforts to develop novel therapies using new chemotherapeutic agents, such as anti-angiogenesis agents and poly (ADP-ribose)-polymerase inhibitors, to improve patient outcomes, the five-year survival for this malignancy remains low. Therefore, it is important to identify new targetable molecules for the early diagnosis, monitoring, and treatment of this malignancy. The aim of this review is to discuss the role of mesothelin in serous ovarian carcinomas, focusing on diagnostic, prognostic, and therapeutic perspectives. ABSTRACT: Mesothelin (MSLN) is a protein expressed in the mesothelial cell lining of the pleura, peritoneum, and pericardium; its biological functions in normal cells are still unknown. Experimental studies using knockout mice have suggested that this molecule does not play an important role in development and reproduction. In contrast, it has been observed that this molecule is produced in abnormal amounts in several malignant neoplasms, such as mesotheliomas and pancreatic adenocarcinomas. Many molecular studies have also demonstrated that mesothelin is overexpressed in HSOCs. Here, we discuss the current knowledge of mesothelin and focus on its role in clinical and pathological diagnoses, as well as its impact on the prognosis of HSOC. Moreover, regarding the binding of MSLN to the ovarian cancer antigen CA125, which has been demonstrated in many studies, we also report on signal transduction pathways that may play an important role in the spread and neoplastic progression of this lethal neoplasm. Given that mesothelin is overexpressed in many solid tumours and has antigenic properties, this molecule could be considered an antigenic target for the treatment of many malignancies. Consequently, we also review the literature to report on mesothelin-targeting therapies for HSOC that have been recently investigated in many clinical studies.