Abstract 4613: Differential TROP2 immunohistochemical expression between pleomorphic and classic invasive lobular carcinoma of the breast

Abstract Background: TROP2, a transmembrane glycoprotein implicated in tumor progression and metastasis, exhibits variable expression across breast cancer subtypes. The classic variant of invasive lobular carcinoma (ILC-C) and the pleomorphic variant (ILC-P) display distinct morphological and biological characteristics. This study aims to investigate differences in TROP2 expression between ILC-C and ILC-P, enhancing our understanding of its potential as a biomarker for aggressive subtypes. Methods: TROP2 protein expression was evaluated in 14 samples (8 ILC-C and 6 ILC-P) using immunohistochemistry (IHC) and quantified with digital image analysis software. Samples were annotated and classified into tumor and stroma components. The percentage of TROP2-positive cells was assessed, and staining intensity was categorized as weak, moderate, or strong. H-scores were calculated to assess overall TROP2 expression. Statistical analyses included descriptive statistics and the Wilcoxon test to compare expression levels between ILC-C and ILC-P groups. Results: TROP2 expression was significantly higher in ILC-P samples compared to ILC-C across multiple metrics. The percentage of positive cells was markedly elevated in ILC-P (mean: 73.04; median: 81.09; SD: 16.08) compared to ILC-C (mean: 17.97; median: 15.14; SD: 12.48). Similarly, H-scores were significantly higher in ILC-P (mean: 153.07; median: 146.79; SD: 54.31) than in ILC-C (mean: 24.97; median: 17.96; SD: 18.81). The Wilcoxon test for both parameters revealed statistical significance (p = 0.002). However, no significant difference was observed between molecular classification groups and TROP2 expression levels. Conclusion: Our findings demonstrate distinct TROP2 protein expression profiles in ILC, with ILC-P samples exhibiting significantly higher expression levels. This elevated TROP2 expression in the aggressive ILC-P variant highlights its potential as a biomarker for identifying high-risk lobular carcinoma subtypes. Further studies are warranted to explore the clinical implications of TROP2 in ILC-P, potentially guiding targeted therapeutic strategies. Citation Format: Elizve Barrientos-Toro, Harsh Batra, Pandurengan Renganayaki, Yasmeen Qamar Rizvi, Jason Aboudi Mouabbi, Funda Funda Meric-Bersntam, Qingqing Ding, Aysegul Sahin, Maria Gabriela Raso. Differential TROP2 immunohistochemical expression between pleomorphic and classic invasive lobular carcinoma of the breast [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4613.