320 Clinical Significance of Mesothelin Expression and Its Correlation with HER2 in Gynecologic Carcinosarcoma

Introduction/Background Mesothelin (MSLN) is a membrane glycoprotein which is highly expressed in many cancers. However, MSLN expression and its prognostic impact in patients with gynecologic carcinosarcoma (GCS) remain unknown. We evaluated MSLN expression in GCS and investigated its associations with clinicopathological characteristics and prognosis in uterine carcinosarcoma (UCS) patients. Additionally, we investigated the correlation between MSLN and HER2, which is one of the promising treatment strategies for GCS. Methodology We examined a cohort of GCS patients who underwent surgery between 1997 and 2019. Immunohistochemical staining was performed for MSLN (SP74) and HER2 (4A5). MSLN expression was scored based on the H-score and a 4-tiered scoring system. MSLN positivity was defined as any positive cell at any intensity, while high MSLN expression was defined as an intensity of ≥2+ in ≥30% of tumor cells. HER2 expression was evaluated following the modified 2018 American Society of Clinical Oncology/College of American Pathologists criteria. Results A total of 128 patients were included in this study, comprising 119 with UCS and 9 with ovarian carcinosarcoma (OCS). All UCS patients were MSLN-positive, with 33.9% showing high expression. Clinicopathological characteristics did not correlate with MSLN expression. However, the high-MSLN group showed significantly longer overall survival (OS) compared to low expression (not reached vs. 36.8 months; HR=0.48, 95% CI=0.26–0.89, p=0.016). HER2-high patients had higher MSLN expression than HER2-negative patients. In both high and low MSLN groups, HER2 status did not impact OS. All patients with OCS showed MSLN positivity, with 66.6% high expression. Conclusion In this study, MSLN expression is widely observed in UCS. Moreover, high-MSLN expression is a favorable prognostic factor for UCS, which could be a promising therapeutic target, regardless of HER2 expression. This study was published in the Journal of Gynecologic Oncology. Disclosures Kan Yonemori- Receipt of grants from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Daiichi-Sankyo, AstraZeneca, Taiho, Pfizer, Novartis, Takeda, Chugai, Ono, Seattle Genetics, Eisai, Eli Lilly, Genmab, Boehringer Ingelheim, Kyowa Hakko Kirin, Nihon Kayaku, Sanofi and Haihe. Receipt of honoraria from Pfizer, Eisai, AstraZeneca, Eli lilly, Takeda, Chugai, MSD, FujiFilm Pharma, Bayer, Asteras, Boehringer Ingelheim, Daiichi Sankyo, PDR Pharma and Sanofi. Tadaaki Nishikawa- Receipt of grants from Daiichi-Sankyo, and AstraZeneca. Receipt of honoraria from AstraZeneca, Chugai, Takeda, MSD, Eisai, Taiho, Roche Diagnostics and Sanofi.