Introduction/Background*Mesothelin (MSLN) is a CA125 binding protein that mediates cell adhesion. This interaction was suggested to play a role in the peritoneal metastasis development. In preclinical models, MSLN overexpression activates the PI3K/AkT, NFκB, and MAPK/ERK pathways, to promote cell proliferation, migration and metastasis. For these reasons, MSLN represents an attractive molecule for targeted ovarian cancer (OC) therapies.

Methodology Paraffin-embedded tumor tissue samples from 113 primary OC patients were selected from TOC biobank (www.toc-network.de) and assessed for the immunohistochemical expression of MSLN on Tissue Microarray. For 51 included HGSOC patients, also paired recurrent samples were available and selected for MSLN evaluation.

All patients were treated at Charité Medical University Berlin, Germany, through primary cytoreduction followed by platinum-based chemotherapy. MSLN expression profiles were correlated with patients’ clinic-pathological and survival data. MSLN expression was also compared between paired primary and recurrent HGSOC samples.

Result(s)*164 samples were assessed for MSLN expression (113 primary OC and 51 recurrent OC).

Among the primary OC cohort, results showed that MSLN(+) samples were 85% of cases (96/113), whereas MSLN was negative in the remaining 15% of cases (17/113). MSLN expression did not differ among different OC histological subtypes (serous, clear cells and endometrioid), but MSLN(+) samples were diagnosed more frequent in the group of advanced FIGO stage (65/96 vs 31/96, p=0.022) and in platinum sensitive patients (85/96 vs 11/96, p=0.001).

Survival analysis showed that MSLN(+) was associated with a significant survival advantage at 5yOS (p=0.022) in HGSOC patients. No survival impact (5yPFS and/or 5yOS) of MSLN expression could be detected for other OC histologies.

Pairwise analysis on paired primary and recurrent HGSOC, also revealed that MSLN(+) tumors were more frequent among primary rather than recurrent HGSOC (46/51 vs 38/51,p=0.012); Furthermore, Spearman test showed a significant correlation among primary and recurrent samples in terms of MSLN expression decrease at recurrence (p=0.003).

Conclusion*Overexpression of MSLN was observed in FIGO advanced stage and in platinum sensitive primary OC patients. MSLN expression was equally distributed among different OC histologies, but in HGSOC conferred survival advantage. Moreover, its expression significantly decreased from primary to recurrent OC.