The Importance of 5-hmC Expression Loss in Diagnosis of Mesothelioma and the Relationship Between TROP2 Expression and Histomorphological Parameters in Mesotheliomas.

ObjectivesMesothelioma is an aggressive cancer that is often not suitable for curative surgery. It can be difficult to distinguish from reactive processes and other malignancies, especially in small biopsies, and outcomes of systemic therapies remain limited. Recently, loss of 5-hydroxymethylcytosine (5-hmC) expression has been shown to aid in differentiate mesothelioma from reactive mesothelial hyperplasia (RMH). Additionally, sacituzumab govitecan, currently approved only for advanced-stage triple-negative breast cancer, is being explored as a promising treatment option for mesothelioma. This study aimed to evaluate the diagnostic accuracy of 5-hmC in differentiating mesothelioma from RMH and to examine the relationship between trophoblast cell surface antigen 2 (TROP2) expression and pathological features in mesothelioma.MethodsThe study included specimens from 30 mesothelioma and 27 RMH patients. Immunohistochemical analysis was performed to assess 5-hmC expression in both groups and TROP2 expression only in mesothelioma. Loss of nuclear 5-hmC expression in ≥50% of cells was used as the diagnostic threshold. TROP2 was evaluated using the -score method.ResultsLoss of ≥50% nuclear 5-hmC expression was significantly more frequent in mesothelioma compared to RMH ( = .015). TROP2 expression showed a significant correlation with high nuclear grade, overall tumor grade, and mitotic figures per 2 mm ( < .05). No significant association was found between TROP2 expression and other histological parameters.ConclusionLoss of ≥50% nuclear 5-hmC is a sensitive and specific marker for distinguishing mesothelioma from RMH. High TROP2 expression in tumors with high mitotic figures and higher nuclear and tumor grade suggests these patients may benefit from sacituzumab govitecan therapy.