Apoptosis of Mesothelial Cells Is Associated with the Pattern of Peritoneal Metastases in Ovarian Cancer

<b>Background/Objectives</b>: Peritoneal carcinomatosis is the leading cause of death in advanced ovarian cancer (AOC). Mesothelial cells lining the peritoneum modulate tumor implantation, yet the role of their apoptosis in metastasis development remains unclear. This study investigated the relationship between mesothelial cell apoptosis and metastatic spread in ovarian cancer (OC). <b>Methods</b>: The study included 26 patients with AOC, 11 with early-stage OC (EOC), and 13 healthy controls. Apoptotic activity in parietal peritoneal wall and omental mesothelial cells was assessed using the TUNEL technique. Metastases were classified as pushing or infiltrating. Associations with the peritoneal cancer index (PCI), BRCA mutation, and homologous recombination deficiency (HRD) status were analyzed. <b>Results</b>: Mesothelial cells adjacent to AOC metastases exhibited significantly higher apoptotic activity compared to controls (<i>p</i> < 0.05). Apoptosis was greater near infiltrating metastases than near pushing ones in both parietal (<i>p</i> < 0.01) and omental (<i>p</i> = 0.04) sites. The infiltration pattern was consistent between omental and parietal metastases (R = 0.588, <i>p</i> < 0.01). No significant differences in apoptosis were found between EOC and healthy controls, or in tumor and stromal cells between invasion types. Mesothelial apoptosis was independent of PCI, BRCA mutation, and HRD status. <b>Conclusions</b>: Our study suggests that mesothelial cell apoptosis may be associated with peritoneal spread in OC. Mesothelial cell apoptosis is more pronounced near infiltrative-type lesions, independent of BRCA/HRD status. These findings highlight mesothelial apoptosis as a relevant process in peritoneal dissemination. Further studies are needed to clarify its role in ovarian cancer progression.