Abstract PO1-13-07: LIV-1 and Trop2 expression using Immunohistochemistry as prognostic markers in early breast cancer
Authors: Choi Yeonjoo , Ryu Han Suk , Koh Jiwon , Lee Dae-Won , Lee Kyung-hun , Im Seock-Ah 
Published: May 2024

Backgrounds: Antibody-drug conjugate (ADC) has emerged as treatment option for breast cancer (BC). The ASCENT and TROPiCS-02 trial of Sacituzumab Govitecan, a Trop2 ADC, gained great success in TNBC and HR+ BC. Other targets, such as LIV-1, are being investigated for TNBC and HR+ BC. The clinical trials of Ladiratuzumab, an ADC of LIV-1 Ab and MMAE, are ongoing. However, unlike Her2 protein, the predictive and prognostic role of LIV-1 and Trop-2 has not been fully investigated. Therefore, we aimed to analyze the relationship between expression level and clinicopathological features and explore the value of the markers among subtypes of BC. Methods: TMA were selected from 1,349 breast cancer specimen of patients who received curative surgery from 2008 to 2012 at Seoul National University Hospital and IHC staining was performed on the TMA using LIV-1 antibody (HPA042377 manufactured by Sigma-Aldrich, St. Louis, MO, dilution ratio of 1:300) and Trop2 antibody(HPA055067, dilution ratio of 1:75). All IHC slides were carefully evaluated by trained pathologists. IHC expression was assessed as intensity (negative:0, weak:1, moderate:2, and strong:3). A modified histochemical score(H-score) was calculated from the intensity multiplied by the percentage of positive cells. Results: A total of 1119 patients from selected samples were included. The median age was 49 (range 25-90). Most patients had early T stage disease (n=513, 569, 29, 7, for pT1, pT2, pT3, pT4, respectively). The percentage of nodal metastasis (N=687 vs 432 in pN0 vs ≥pN1, 61.4 vs 38.6%) and LVI (N= 678 vs 441 in neg vs pos, 60.6% vs 38.6%). 713 pts (63.7%) were HR+ subtype, 200(17.9%) of Her2+ and 206(18.4%) of TNBC. We divided patients into negative/low/high expression groups according to LIV-1 expression by median expression level (cutoff H-score = 100): 479 of 1119 (42.8%) LIV-1-negative; 270 (42.2%) LIV-1-low expression and 370 (57.8%) LIV-1-high. Patients with LIV-1-low or -high tumors showed better DFS (156.2 vs 158.8 vs 159.95 mo for LIV-1-negative, -low, -high, respectively; P=0.0072) and OS(157.6 vs 163 vs 165.4 mo, P=0.0029) . HR+ subgroup, (N= 193 vs 228 vs 354 for neg vs low vs high), followed overall tendency (153.4vs 158.3 vs 159.9mo, P=0.0571 in DFS, 155.6vs160.2 vs165.4mo, P=0.0627 in OS, respectively) In contrast, for patients with TNBC, LIV-1-high expression showed the worst DFS and OS. (N = 183 vs 18 vs 5 in neg vs low vs high group, 159.7 vs 160.7 vs 93.1mo, P value=0.1854 for DFS, 160.8 vs 160.7 vs 93.1 mo, P=0.0334 for OS, respectively) LIV-1 expression failed to prove a prognostic value in Her2+ BC. We also analyzed Trop2 expression by dividing patients into low/intermediate/high by the method used previously in ASCENT trial. 1009 of 1119 (n=341 in low, 363 in intermediate, 305 in high expression) patients had Trop2 expression. There was no statistically significant difference in DFS and OS among all subtypes. In multivariate analysis, neither LIV-1 or Trop-2 had a prognostic role. Conclusion: The analysis of clinicopathological findings of LIV-1 protein indicates their values for prognosis markers, especially in HR+ BC and TNBC. Trop2 expression has no prognostic role in line with previous research. Further studies are warranted to explore targetable biomarkers for the development of appropriate ADCs.

Citation Format: Yeonjoo Choi, Han Suk Ryu, Jiwon Koh, Dae-Won Lee, Kyung-hun Lee, Seock-Ah Im. LIV-1 and Trop2 expression using Immunohistochemistry as prognostic markers in early breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-13-07.