High Trop-2 expression in pulmonary sarcomatoid carcinoma reveals antibody-drug conjugate targeting Trop-2 is a promising therapeutic approach.

BACKGROUND: Several antibody-drug conjugates (ADC) targeting Trophoblast cell surface antigen 2 (Trop-2) have been developed, demonstrating significant therapeutic efficacy in triple-negative breast cancer and non-small cell lung cancer. However, the current expression of Trop-2 in pulmonary sarcomatoid carcinoma (PSC) and its clinical prognostic significance remains unclear. MATERIALS AND METHODS: Surgical tissue specimens diagnosed with PSC from January 2015 to May 2023 were retrospectively collected to detect Trop-2 expression using immunohistochemistry. The semi-quantitative H-score was employed to evaluate Trop-2 expression (< 10 is 0, 10-40 is 1 + , 41-140 is 2+, and 141-300 is 3+). We evaluated Trop-2 expression in PSC patients, comparing expression levels between the carcinomatous component (CaC) and the sarcomatous component (SaC), and analyzed their associations with clinicopathological characteristics and prognosis. RESULTS: Thirty-five PSC patients receiving curative surgical resection were enrolled. The median disease-free survival (DFS) in PSC patients was 15.7 (95% CI 7.0-24.4) months, while the median overall survival was not reached. Positive expression of Trop-2 was observed in 31 (88.6%) PSC patients, the frequencies of 1+, 2+, and 3+ were 28.6%, 42.9%, and 17.1%, respectively. In 25 PSC patients with both CaC and SaC, we found a difference in Trop-2 expression between the two components (CaC vs. SaC, 100% vs. 56.0%). The intratumoral heterogeneity (ITH) of Trop-2 expression was not associated with clinicopathologic features. Patients in the CaC+/SaC+ group demonstrated significantly poorer DFS compared to the CaC+/SaC- group (12.5 months vs. > 60.0 months, p = 0.045). Multivariate Cox regression analysis indicated that an ECOG score of ≥ 1 (p = 0.004), stage II (p = 0.032), and CaC+/SaC+ (p = 0.030) were independently associated with a shorter DFS. CONCLUSION: The level of Trop-2 expression was high in PSC patients, and there is ITH in its expression. Targeting Trop-2 therapies may be a promising treatment for patients with PSC.