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Background <p>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.</p> Materials and methods <p>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 (&lt; 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.</p> Results <p>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&#xa0;months vs. &gt; 60.0&#xa0;months, <i>p</i> = 0.045). Multivariate Cox regression analysis indicated that an ECOG score of ≥ 1 (<i>p</i> = 0.004), stage II (<i>p</i> = 0.032), and CaC+/SaC+ (<i>p</i> = 0.030) were independently associated with a shorter DFS.</p> Conclusion <p>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.</p>

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

  • 期刊论文

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  • 发表日期：

    2025年7月30日

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  • Xiaoying Qian,
  • Chuanhong Luo,
  • Chen Fang,
  • Yongbin Wu,
  • Weiwei Hong,
  • Biao Yu,
  • Guizhen Qin,
  • Yan Yin,
  • Xinyuan Yao,
  • Xin Ye,
  • Bingbiao Zhou,
  • Chengsi Shu,
  • Dengying Chen,
  • Zhaoqing Li,
  • Shanshan Wang,
  • Yong Wang,
  • Yong Li

摘要

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.