J Gynecol Oncol.  2024 Mar;35(2):e11. 10.3802/jgo.2024.35.e11.

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

• Kitadai R
• Nishikawa T
• Yoshida H
• Mizoguchi C
• Yamamoto K
• Kato T
• Yonemori K

• KMID: 2564871
• DOI: http://doi.org/10.3802/jgo.2024.35.e11

Abstract

Objective
This study aimed to evaluate mesothelin (MSLN) expression and determine its clinical 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 underwent surgery 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-score and 4-tired scoring system (0–3+). 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 scored according to modified 2018 American Society of Clinical Oncology/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-MSLN expression. However, the high-MSLN group showed more prolonged overall survival (OS) than the low-MSLN group (not assessed vs. 36.8 months; hazard ratio=0.48, 95% confidence interval=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 not affect OS. OCS showed 100% MSLN positivity, with 66.6% high-MSLN.
Conclusion
MSLN expression is widely observed in gynecological carcinosarcomas. Moreover, high-MSLN expression is a favorable prognostic factor for UCS. MSLN could be a promising therapeutic target for UCS, even in the era of anti-HER2 therapy.

Keyword

Uterine Carcinosarcoma; Ovarian Carcinosarcoma; Mesothelin; Human Epidermal Growth Factor Receptor 2; Immunohistochemistry; Prognosis