Mesothelin expression in gynecologic carcinosarcoma: clinicopathological significance and correlation with HER2expression
	    		
		   		
		   			
		   		
	    	
    	- Author:
	        		
		        		
		        		
			        		Rui KITADAI
			        		
			        		
			        		
			        			1
			        			
			        		
			        		
			        		
			        		
			        		;
		        		
		        		
		        		
			        		Tadaaki NISHIKAWA
			        		
			        		;
		        		
		        		
		        		
			        		Hiroshi YOSHIDA
			        		
			        		;
		        		
		        		
		        		
			        		Chiharu MIZOGUCHI
			        		
			        		;
		        		
		        		
		        		
			        		Kasumi YAMAMOTO
			        		
			        		;
		        		
		        		
		        		
			        		Tomoyasu KATO
			        		
			        		;
		        		
		        		
		        		
			        		Kan YONEMORI
			        		
			        		
		        		
		        		
		        		
			        		
			        		Author Information
			        		
 - Publication Type:Original Article
 - From:Journal of Gynecologic Oncology 2024;35(2):e11-
 - CountryRepublic of Korea
 - Language:English
 - 
		        	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. 
            