Abstract 361: Mesothelin expression varies by histological type in patients with cervical cancer and is reduced in metastatic tumors
Authors: Yazaki Shu , Kojima Yuki , Yoshida Hiroshi , Kitadai Rui , Takamizawa Shigemasa , Shimoi Tatsunori , Nishikawa Tadaaki , Sudo Kazuki , Kato Tomoyasu , Yonemori Kan 
Published: July 2021

Abstract
Background: Mesothelin (MSLN) is a cell-surface glycoprotein highly expressed in many cancers, while its expression is limited to normal mesothelial cells. Aberrant MSLN expression is considered to play an essential role in promoting proliferation, cell migration, and invasion. Early phase clinical trial of the antibody-drug conjugate of anti-MSLN-antibody demonstrated patients who responded to treatment had high MSLN expression. Hence, MSLN is an attractive target for cancer therapy. However, the association between MSLN expression and clinicopathologic features in cervical cancer has not been clarified.
Methods: This retrospective study included patients diagnosed with cervical cancer who underwent primary surgery between 2000 and 2020. The VENTANA MSLN (SP74) IHC assay was used to assess MSLN expression. The MSLN positive was defined as the tumors expressing MSLN at any intensity. Tumors were considered high MSLN expression if MSLN was detected at a 2+ or 3+ intensity on ≥30% of tumor cells. The association of MSLN expression with overall survival was assessed by multivariate cox regression analysis, adjusting for established prognostic factors.
Results: Overall, 123 patients were enrolled, and 140 tumor samples (17 paired primary and metastatic samples) were evaluated. The histopathologic classification was squamous cell carcinoma (Sq)/adenocarcinoma (Ad)/adenosquamous carcinoma (Adsq)/adenocarcinoma, gastric type (Ga)/neuroendocrine carcinoma=67/27/13/12/4. MSLN-positive was found in 95.7% (134/140), and MSLN-high was 48% (36/75) of Sq and 86.5% (45/52) of Ad/Adsq/Ga. An analysis of the Cancer Genome Atlas (TCGA) cervical cancer dataset (N=280) confirmed that a higher level of MSLN mRNA expression in Ad compared to Sq (log fold-change 3.13, p&lt;0.001). The high MSLN expression was not associated with tumor size, FIGO stage, lymph node metastasis, and distant metastasis. The median overall survival tended to be shorter in the MSLN-high group than in the MSLN-low group (hazard ratio [HR] 3.19, 95% confidence interval [CI] 0.86-11.8, p=0.08). The analysis of matched primary and metastatic tumors showed no significant difference in the median H-score of MSLN expression between primary and metastatic tumors (80 in primary vs. 50 in metastatic, p=0.2). However, among the patients who were MSLN-high at the primary site, 37.5% (3/8) were MSLN-low at the metastases.
Conclusion: MSLN was highly expressed in cervical adenocarcinoma, including adenosquamous carcinoma and adenocarcinoma, gastric type. Despite the MSLN-high in the primary tumor, MSLN expression was reduced in metastatic tumors in 37.5% of patients. The MSLN may be a potential target for cervical adenocarcinoma, and reassessment of MSLN expression at metastatic sites is desirable to maximize the therapeutic effects.
Citation Format: Shu Yazaki, Yuki Kojima, Hiroshi Yoshida, Rui Kitadai, Shigemasa Takamizawa, Tatsunori Shimoi, Tadaaki Nishikawa, Kazuki Sudo, Tomoyasu Kato, Kan Yonemori. Mesothelin expression varies by histological type in patients with cervical cancer and is reduced in metastatic tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 361.