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. 2022 May 30;29(6):3911-3921.
doi: 10.3390/curroncol29060312.

Trop-2 in Upper Tract Urothelial Carcinoma

Eisuke Tomiyama  1 , Kazutoshi Fujita  1   2 , Kosuke Nakano  1 , Ken Kuwahara  2 , Takafumi Minami  2 , Taigo Kato  1 , Koji Hatano  1 , Atsunari Kawashima  1 , Motohide Uemura  1 , Tetsuya Takao  3 , Hiroaki Fushimi  4 , Kotoe Katayama  5 , Seiya Imoto  5   6 , Kazuhiro Yoshimura  2 , Ryoichi Imamura  1 , Hirotsugu Uemura  2 , Norio Nonomura  1
Affiliations

Trop-2 in Upper Tract Urothelial Carcinoma

Eisuke Tomiyama et al. Curr Oncol. .

Abstract

Trophoblast cell surface antigen 2 (Trop-2, encoded by TACSTD2) is the target protein of sacituzumab govitecan, a novel antibody-drug conjugate for locally advanced or metastatic urothelial carcinoma. However, the expression status of Trop-2 in upper tract urothelial carcinoma (UTUC) remains unclear. We performed immunohistochemical analysis of 99 UTUC samples to evaluate the expression status of Trop-2 in patients with UTUC and analyze its association with clinical outcomes. Trop-2 was positive in 94 of the 99 UTUC samples, and high Trop-2 expression was associated with favorable progression-free survival (PFS) and cancer-specific survival (p = 0.0011, 0.0046). Multivariate analysis identified high Trop-2 expression as an independent predictor of favorable PFS (all cases, p = 0.045; high-risk group (pT3≤ or presence of lymphovascular invasion or lymph node metastasis), p = 0.014). Gene expression analysis using RNA sequencing data from 72 UTUC samples demonstrated the association between high TACSTD2 expression and favorable PFS (all cases, p = 0.069; high-risk group, p = 0.029). In conclusion, we demonstrated that Trop-2 is widely expressed in UTUC. Although high Trop-2 expression was a favorable prognostic factor in UTUC, its widespread expression suggests that sacituzumab govitecan may be effective for a wide range of UTUC.

Keywords: RNA sequencing; TACSTD2; immunohistochemical analysis; sacituzumab govitecan; trophoblast cell surface antigen 2; upper tract urothelial carcinoma.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Immunohistochemical expression of trophoblast cell surface antigen 2 (Trop-2) in upper tract urothelial carcinoma (UTUC) tissue microarray specimens. UTUC tissue with (A) high (3+), (B) moderate (2+), (C) low (1+), and (D) negative (0+) expression.
Figure 2
Figure 2
(A) Progression-free survival and (B) cancer-specific survival of 99 patients with upper tract urothelial carcinoma stratified using expression of trophoblast cell surface antigen 2 (Trop-2, 0/1+/2+ vs. 3+).
Figure 3
Figure 3
(A) Progression-free survival and (B) cancer-specific survival of 60 patients with high-risk upper tract urothelial carcinoma (with a pathologic stage of ≥pT3 or positive lymphatic invasion or lymph node metastasis) stratified using expression of Trop-2 (0/1+/2+ vs. 3+).
Figure 4
Figure 4
Progression-free survival in (A) 72 patients with upper tract urothelial carcinoma (UTUC) and (B) 33 patients with high-risk UTUC (with a pathologic stage of ≥pT3 or positive lymphatic invasion or lymph node metastasis) stratified using expression of TACSTD2 gene (high vs. low).
See this image and copyright information in PMC

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