Immunohistochemical expression of TROP‑2 (TACSTD2) on the urothelial carcinoma of the urinary bladder and other types of cancer

Abstract

In metastatic or locally advanced urothelial carcinoma (UC), therapeutic options have been limited to chemotherapy and immune checkpoint inhibitors. Novel targets and drugs such as antibody drug conjugates have been developed, and enfortumab vedotin targeting nectin-4 and sacituzumab govitecan (SG) targeting trophoblast cell surface antigen 2 (TROP-2), the protein product of the TACSTD2 gene, have been approved. The expression of TROP-2 was investigated within UC and other types of carcinomas, and within the tissue of different healthy organs to understand treatment responses and toxicities. The expression of TROP-2 in the tissues of 42 patients with UC, 13 patients with other types of cancer and in the normal tissues of 11 patients was retrospectively analyzed. Immunohistochemical staining of the TROP-2 protein was performed on a BenchMark ULTRA IHC/ISH System (Roche Tissue Diagnostics; Roche Diagnostics, Ltd.) according to accredited staining protocols in a routine immunohistochemistry accredited and certified facility of the laboratory of immunohistochemistry at the Institute of Pathology (Gerhard-Domagk Institute)- University Hospital Muenster (UKM)-Muenster-Germany]. Different expression levels of TROP-2 were observed, and the highest expression rate of TROP-2 was observed in UC, independent of the tumor stage. However, normal urothelial cells had similar expression levels. Except for ductal carcinoma in situ, the expression of TROP-2 was reduced in other types of cancer and in the healthy tissues from other organs, including pancreas, gall bladder, colon and prostate. Given the treatment response based on the expression level of TROP-2, SG would be effective in almost all cases of UC. However, it would also have an effect on the normal urothelium.

Keywords: antibody drug conjugate; sacituzumab govitecan; trophoblast cell surface antigen 2; urothelial carcinoma.

Figure 1.

Immunohistochemical expression of TROP-2 on different subtypes of uothelial carcinoma of the urinary bladder and renal pelvis, normal urothelium and non-invasive urothelial tumors. (A-C) Normal urothelial cells of the bladder with strong expression of TROP-2 (3+) on the surface of 100% of the cells (magnification, ×10). (D) Invasive UC of the bladder with strong expression of TROP-2 (3+) on the membrane of 100% of the tumor cells (magnification, ×10). (E) Invasive high-grade neuroendocrine carcinoma of the bladder with strong expression of TROP-2 on the membrane and in cytoplasm in the central group of tumor cells (magnification, ×10). (F) Invasive UC of the renal pelvis with strong expression of TROP-2 (3+) on the membrane of 100% of the tumor cells (magnification, ×10). (G) Papillary non-invasive UC of the bladder with strong expression of TROP-2 (3+) on the surface of 100% of the tumor cells (magnification, ×10). (H) Papillary non-invasive UC of the bladder with papillary projections of the neoplastic urothelial cells (magnification, ×10; stained with H&E). (I) Urothelial CIS of the bladder with flat lesions of the dysplastic urothelial cells (magnification, ×20; stained with H&E). (J) Urothelial CIS of the bladder with strong expression of TROP-2 (3+) on the surface of 100% of the tumor cells (magnification, ×20). TROP-2, trophoblast cell surface antigen 2; UC, urothelial carcinoma; H&E, hematoxylin and eosin; CIS, carcinoma in situ.

Figure 2.

Expression of TROP-2 on the primary and metastatic prostate carcinoma, normal prostatic tissue and other non-urogenital organs. (A) Primary PC with moderate expression of TROP-2 (2+) on the cell membrane of 100% of the tumor cells. Normal cells of the seminal vesicle have strong expression of TROP-2 (3+) on the membrane of 100% of the cells (magnification, ×10). (B) Primary PC with weak expression of TROP-2 (1+) on the cell membrane of 100% of the tumor cells of Gleason grade 3, but no TROP-2 expression on the tumor cells of Gleason grade 4 in the middle of the field (magnification, ×10). (C) Normal prostate tissue with strong expression of TROP-2 (3+) on the surface of 100% of the glandular epithelial cells (magnification, ×20). (D) Metastatic PC in a lymph node with strong expression of TROP-2 (3+) on the cell membrane of 100% of the tumor cells (magnification, ×10). (E) On the right, there is no expression of TROP-2 in invasive colon adenocarcinoma. On the left, there is also no expression of TROP-2 in non-neoplastic colon mucosa (magnification, ×10). (F) Normal pancreatic tissue with weak expression of TROP-2 (1+) on the cell membrane of acinar cells (magnification, ×10). (G) Weak expression of TROP-2 (1+) on the membrane of cells of invasive endometrial glands (magnification, ×10). (H) Normal epithelium of the gall bladder with moderate expression of TROP-2 (2+) on the surface of ~10% of the normal glandular epithelium (magnification, ×10). (I) Intraluminal cells of ductal carcinoma in situ of the breast demonstrated moderate expression of TROP-2 (2+) on the membrane of 100% of the cells. Cells of normal glands and ducts presented in the same section on the lefthand side had strong expression of TROP-2 (3+) on the cell membrane (magnification, ×4). PC, prostate carcinoma; TROP-2, trophoblast cell surface antigen 2.