Abstract 2034: Investigation of TROP2 expression and immune microenvironment in ovarian clear cell carcinoma

Abstract Background: Ovarian clear cell carcinoma (OCCC) is a rare subtype of ovarian cancer, with a higher incidence in East Asia compared to Western countries and a tendency to affect younger individuals. OCCC has poor prognosis due to its low sensitivity to chemotherapy, presenting a significant unmet medical need. However, therapeutic development has been limited due to its rarity. Recently, advancements in antibody-drug conjugates (ADCs) targeting Trophoblastic cell-surface marker (TROP2) have shown promise, but the expression of these therapeutic targets in OCCC remains unclear. This study aimed to explore new therapeutic targets for OCCC by analyzing TROP2 expression and the immune microenvironment. Methods: Clinical data were collected from OCCC patients who underwent surgery at the National Cancer Center Hospital between 2007 and 2024. TROP2 (MAB650), ARID1A (polyclonal), and PD-L1(E1L3N) were evaluated. PD-L1 expression was evaluated using both Tumor Proportion Score (TPS) and Combined Positive Score (CPS). TROP2 expression was assessed using the H-score, with a score of ≥10 defined as positive. Pathological features, including stromal characteristics, cytoplasmic features, and tissue architecture, were also analyzed. Results: A total of 125 OCCC patients were included. TROP2 expression was positive in 90 patients (72.0%) and negative in 35 patients (28.0%). ARID1A was retained in 52 patients (41.6%) and lost in 73 patients (58.4%). TPS values were <1 in 44 patients (35.2%), 1-49 in 73 patients (58.4%), and ≥50 in 8 patients (6.4%). CPS values were <1 in 33 patients (26.4%), 1-9 in 30 patients (24.0%), and ≥10 in 62 patients (49.6%). No significant differences were observed in TROP2 expression across these variables. Overall survival did not significantly differ between TROP2-positive and TROP2-negative patients (HR=1.22, 95%CI: 0.48-3.09, p=0.67). ARID1A status was also not associated with survival (HR=1.48, 95%CI: 0.62-3.49, p=0.37). However, CPS ≥10 was associated with a trend toward worse prognosis (HR=2.92, 95%CI: 0.95-8.41, p=0.06). Poor prognosis was also observed in cases with high stromal inflammation (HR=2.47, 95%CI: 1.09-5.60, p=0.03) and solid tissue architecture (HR=2.89, 95%CI: 0.99-8.46, p=0.05). Patients with both CPS ≥10 and TROP2 positivity accounted for 47 individuals (37.6%) and showed a trend toward worse prognosis compared to CPS-negative and TROP2-negative patients (HR=3.17, 95%CI: 0.71-14.06, p=0.13). Conclusions: In OCCC, 72% of patients exhibited TROP2 positivity, and 49.6% had CPS ≥10. Patients with CPS positivity tended to have worse prognosis, and those with both TROP2 and CPS positivity represented 37.6% of the cohort. These findings suggest that TROP2-ADC and combination immunotherapy may represent promising therapeutic strategies for this patient subgroup. Citation Format: Toru Imai, Yuki Kojima, Hiroshi Yoshida, Rui Kitadai, Mai Hoshino, Ayumi Saito, Munehiro Ito, Shosuke Kita, Aiko Maejima, Kazuki Sudo, Masaya Uno, Tatsunori Shimoi, Mitsuya Ishikawa, Kan Yonemori. Investigation of TROP2 expression and immune microenvironment in ovarian clear cell carcinoma [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 2034.