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        Mesothelin expression in gynecologic carcinosarcoma: clinicopathological significance and correlation with HER2 expression

        Rui Kitadai,Tadaaki Nishikawa,Hiroshi Yoshida,Chiharu Mizoguch,Kasumi Yamamoto,Tomoyasu Kato,Kan Yonemori 대한부인종양학회 2024 Journal of Gynecologic Oncology Vol.35 No.2

        Objective: This study aimed to evaluate mesothelin (MSLN) expression and determine itsclinical significance and correlation with human epidermal growth factor receptor 2 (HER2)expression in gynecological carcinosarcoma. Methods: We retrospectively evaluated patients with uterine carcinosarcoma (UCS)and ovarian carcinosarcoma (OCS) who under went surger y between 1997 and 2019. Immunohistochemical staining of formalin-fixed, paraffin-embedded specimens for MSLN(clone SP74) and HER2 (clone 4A5) was also performed. MSLN was scored using the H-scoreand 4-tired scoring system (0–3+). MSLN positivity was defined as any positive cell at anyintensity, while high MSLN expression was defined as an intensity of ≥2+ in ≥30% of tumorcells. HER2 expression was scored according to modified 2018 American Society of ClinicalOncology/College of American Pathologists criteria. Results: A total of 128 patients were recruited, including 119 with UCS and 9 with OCS. All cases in UCS exhibited MSLN positivity, and 33.9% showed high-MSLN expression. Clinicopathological characteristics were not significantly associated with high or low-MSLNexpression. However, the high-MSLN group showed more prolonged overall sur vival (OS)than the low-MSLN group (not assessed vs. 36.8 months; hazard ratio=0.48, 95% confidenceinter val=0.26–0.89, p=0.016). HER2-high patients had higher MSLN expression than HER2-negative patients. In high-MSLN and low-MSLN expression groups, HER2 status did notaffect OS. OCS showed 100% MSLN positivity, with 66.6% high-MSLN. Conclusion: MSLN expression is widely obser ved in gynecological carcinosarcomas. Moreover, high-MSLN expression is a favorable prognostic factor for UCS. MSLN could be apromising therapeutic target for UCS, even in the era of anti-HER2 therapy.

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