TROP2 expression is abundant in primary and recurrent prostate cancer

The membrane glycoprotein Trophoblast cell surface antigen 2 (TROP2) is the molecular target of sacituzumab govitecan (SG), an antibody-drug conjugate that has been approved for treatment of breast cancer and urothelial carcinomas. To assess the prevalence and clinical significance of TROP2 expression in primary and recurrent prostate cancer, a tissue microarray containing 17,627 primary and 258 recurrent prostate cancer samples was analyzed by immunohistochemistry (IHC). A positive TROP2 immunostaining was seen in 100% of 12,807 interpretable primary prostate cancers and was rated strong in 94.5%, moderate in 3.5%, and weak in 2.0% of cases. The intensity of TROP2 staining decreased significantly with high tumor stage and Gleason grade. Among 12,669 evaluable primary prostate cancers, TROP2 staining was strong in 95.3% of pT2, 94.0% of pT3a, and 93.2% of ≥pT3b (p=0.0011) as well as in 95.2% of Gleason 3+3, 95.8% of Gleason 3+4, 92.7% of Gleason 4+3, and 90.2% of Gleason ≥8 (p<0.0001). Among 250 evaluable recurrent prostate cancers, TROP2 staining was strong in 57.6%, moderate in 31.6%, weak in 8.4%, and negative in 2.4%. Accordingly, TROP2 staining was significantly less intense in recurrent prostate cancer than in primary tumors (p<0.0001) and also less intense than in Gleason ≥8 primary cancers (p<0.0001). Among primary prostate cancers, TROP2 staining was significantly more intense in cancers harboring the TMPRSS2:ERG fusion (98.8% moderate or strong positivity) than in ERG fusion negative tumors (97.5%; p<0.0001). Low TROP2 expression was significantly linked to early biochemical (PSA) recurrence in ERG positive (p=0.0165) but not in ERG negative cancers (p=0.3271). A comparison with 11 of the most frequent genomic deletions ( PTEN , 3p13, 5q21, 6q15, 13q14, 18q21, 8p21, 12p13, 12q24, 16q24, 17p13) did only reveal marginal associations of reduced TROP2 expression with deletions of 6q15 and 8p21 in ERG negative and with 17p13 and PTEN in ERG positive cancers. It is concluded from our data, that TROP2 is always expressed at significant levels in newly diagnosed prostate cancers and that a significant expression is retained in most recurrent cancers although reduced levels of TROP2 expression occur commonly after systemic therapy. Absence of strong associations with chromosomal deletions argues against a relationship between TROP2 expression levels and genomic instability.