Abstract PS18-37: Loss of Trop2 protein in metaplastic carcinoma of breast by IHC
Authors: Yang Fei , Rizvi Yasmeen , Yuca Erkan , Zhao Ming , Evans Kurt , Zheng Xiaofeng , Sahin Aysegul , Meric-Bernstam Funda 
Published: February 2021

Abstract
Background: Trop2 (trophoblast cell surface antigen) is a transmembrane calcium transducer which has been associated with tumor growth, aggressiveness and metastasis. Compared to normal tissue, Trop2 is expressed at much higher levels in many epithelial tumors, which makes it an excellent target for ADCs (antibody-drug conjugates). Sacituzumab govitecan-hziy, an ADC that combines Trop-2 antibody with a SN-38 payload has been recently approved for treatment of refractory metastatic triple-negative breast cancer, and several other TROP2 targeted therapies are in development. To better understand Trop 2 expression in breast tumor that may help to identify patients who could benefit most from Trop2-targeted therapy, we aimed to screen Trop2 protein in multiple types of breast tumor. Design: Using chromogenic immunohistochemistry (IHC), Trop2 protein was examined in 42 formalin fixed paraffin embedded (FFPE) specimens from surgically resected breast tumors, including 21 TNBC, 16 HR+, 4 HER2+ (3 HR+/HER2+ and 1 HR-/HER2+), and 1 sarcoma. Sections were stained on an automated staining system (BOND-MAX; Leica Microsystems) using anti-TROP2 antibody (clone ERP20043, Abcam, cat# 214488). Membrane staining was assessed. The percentage of positivity (0% to 100%) and the staining intensity (0 = no staining, 1+ = weak staining, 2+ = moderate staining, and 3+ = strong staining) were evaluated and multiplied to generate H-score (0-300). Results: Among of 41 breast carcinoma cases, 38 (92.6%) cases expressed Trop2 protein in tumor cells, with a median H-score of 162.5, including 18/21 TNBC, 16/16 HR+, 4/4 HER2+ cases. Trop2 was expressed in several breast cancer histopathology subtypes, including 32 invasive ductal carcinomas (H score ranged from 29 - 290), 2 invasive lobular carcinomas (H score 140 and 145), 1 invasive papillary carcinoma (H score 70), 1 invasive micropapillary carcinoma (H score 210), 1 invasive squamous cell carcinoma (H score 245) and 1 metaplastic carcinoma with mesenchymal differentiation (cartilaginous sarcomatoid type) (H score 17). Three breast carcinomas were negative for Trop2 (H score 0). All three cases are metaplastic carcinomas, including two spindle cell carcinomas and one with mesenchymal differentiation, which are TNBC. Only two of 5 (40%) metaplastic carcinomas tested expressed Trop2 (p = 0.0034). One breast sarcoma was tested and had no TROP2 expression. Conclusion: Trop2 is commonly expressed in breast cancer. However, metaplastic carcinoma of breast has shown a trend of Trop2 protein loss. Further validation on Trop2 loss in metaplastic carcinoma might help with identifying breast cancer patients less likely to benefit from Trop2-targeted therapy.
Citation Format: Fei Yang, Yasmeen Rizvi, Erkan Yuca, Ming Zhao, Kurt Evans, Xiaofeng Zheng, Aysegul Sahin, Funda Meric-Bernstam. Loss of Trop2 protein in metaplastic carcinoma of breast by IHC [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS18-37.