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2022-RA-793-ESGO TROP-2 expression and the tumor immune-microenvironment in cervical cancer
  1. Yohei Chiba1,
  2. Shu Yazaki1,
  3. Yuki Kojima1,
  4. Hiroshi Yoshida2,
  5. Shigemasa Takamizawa1,
  6. Rui Kitadai1,
  7. Ayumi Saito1,
  8. Hitomi Sumiyoshi Okuma1,
  9. Tadaaki Nishikawa1,
  10. Tatsunori Shimoi1,
  11. Kazuki Sudo1,
  12. Emi Noguchi1,
  13. Masaya Uno3,
  14. Mitsuya Ishikawa3,
  15. Tomoyasu Kato3,
  16. Yasuhiro Fujiwara1 and
  17. Kan Yonemori1
  1. 1Medical Oncology, National Cancer Cencer Hopital, Tokyo, Japan
  2. 2Diagnostic Pathology, National Cancer Cencer Hopital, Tokyo, Japan
  3. 3Gynecology, National Cancer Cencer Hopital, Tokyo, Japan


Introduction/Background Trophoblast Cell Surface Antigen 2 (TROP-2) is a transmembrane glycoprotein that is overexpressed in various cancers. Moreover, TROP-2 has immunologic relevance, as a target for tumor reactive T-cells. We performed a pilot study of 123 cervical cancers to test whether TROP-2 expression may be associated with tumor immune-microenvironment.

Methodology We performed immunohistochemical analysis of whole tumor sections from patients with cervical cancer who underwent primary surgery between 2000 and 2020 at our institution. TROP-2 expression was evaluated using anti-TROP-2 monoclonal antibody clone MAB650. Immune biomarkers including PD-L1 (22C3), CD3 (PS1), and CD8 (4B11) were also evaluated. TROP-2 and PD-L1 positive was defined as H-score ≥10 and combined positive score (CPS) ≥1, respectively. Each whole tumor section was evaluated for intratumoral tumor-infiltrating lymphocytes (TILs) by using a 40× objective lens, and 5 independent areas with the most abundant TILs were selected. The association between TROP-2 expression and immune biomarkers was analyzed.

Results The cohort consisted of squamous cell carcinoma (SCC) (54.5%) and non-SCC (45.5%). In IHC samples, TROP-2 positive was identified in 84.6% and more commonly expressed in SCC (SCC vs. non-SCC; 97.0% vs. 69.6%, p<0.001). Spearman’s correlation analysis showed significant and positive correlations between TROP-2 H-score and immune markers (CD3+TILs, r=0.295, p<0.001; CD8+TILs, r=0.267, p=0.001; PD-L1 CPS, r=0.178, p=0.025). None of the other clinicopathological features were associated with T cell infiltration in the study sample. The percentage of TROP2-positive patients in the PD-L1-positive or CD3-High group was 89.2% and 93.9%, respectively. After a median follow-up of 67.8 months, TROP-2 expression showed no correlation with DFS and OS (log rank test, p =0.478 and 0.071).

Conclusion Expression of TROP-2 in cervical cancer is associated with increased levels of intratumoral TILs, indicating the potential therapeutic target for TROP-2 targeted antibody-drug conjugate alone or in combination with immune checkpoint inhibitors.

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