TRPS1 expression in primary and metastatic prostatic adenocarcinoma, muscle invasive bladder urothelial carcinoma, and breast carcinoma: Is TRPS1 truly specific and sensitive for a breast primary?

Trichorhinophalangeal syndrome type 1 (TRPS1) has been reported to be a sensitive and specific immunohistochemical (IHC) marker for breast carcinomas, especially when determining primary site of origin. However, there is limited data on TRPS1 expression in prostate and bladder cancers. A two-phase study was performed with 1) an exploratory cohort analyzing TRPS1 gene alterations in prostate, bladder, and breast carcinoma and TPRS1 mRNA expression data in prostate and bladder carcinoma; and 2) TRPS1 and GATA3 IHC in a confirmatory cohort in prostate, bladder, and breast carcinoma samples. Gene alterations were identified in a subset of breast, bladder, and prostate carcinomas and mRNA was consistently detected. In the IHC cohort, 183/210 (87.1 %) of breast, 22/69 (31.9 %) of prostate, and 20/73 (27.4 %) of urothelial carcinomas showed staining with TRPS1. Intermediate to high expression of TRPS1 was observed in 173/210 (82.8 %) of breast, 17/69 (24.6 %) of prostate, and 15/73 (20.5 %) of urothelial carcinomas. Furthermore, in prostate cancer, 26.9 % of pelvic lymph node metastases and 50 % in sites of distant metastases showed expression. Increased TRPS1 mRNA expression (p = 0.032) and IHC expression (p = 0.040) correlated with worse overall survival in bladder cancer. By comparison, GATA3 IHC stained 136/210 (64.8 %) of breast, 0/69 (0 %) of prostate, and 63/73 (93 %) of bladder carcinomas. Intermediate to high expression of GATA3 was seen in 131/210 (62.4 %) of breast and 63/73 (93 %) of bladder carcinomas. This study shows there is significant staining of TRPS1 in bladder and prostate cancers. As a result, comprehensive studies are needed to establish the true specificity of TRPS1 IHC stain across various tumor types before its widespread clinical adoption.

Human pathology. 2023 Dec 03 [Epub ahead of print]

S Emily Bachert, Jing Di, Shengyi Zhang, Heather E Short, Dava W Piecoro, Robert J McDonald, Zin W Myint, Patrick J Hensley, Derek B Allison

Department of Pathology, Brigham and Women's Hospital, Boston, MA, 02115, USA. Electronic address: ., Department of Pathology and Laboratory Medicine, University of Kentucky College of Medicine, Lexington, KY, 40536, USA. Electronic address: ., Department of Computer Science, University of Kentucky College of Engineering, Lexington, KY, 40536, USA. Electronic address: ., Department of Pathology and Laboratory Medicine, University of Kentucky College of Medicine, Lexington, KY, 40536, USA. Electronic address: ., Department of Pathology and Laboratory Medicine, University of Kentucky College of Medicine, Lexington, KY, 40536, USA. Electronic address: ., Department of Pathology and Laboratory Medicine, University of Kentucky College of Medicine, Lexington, KY, 40536, USA. Electronic address: ., Department of Internal Medicine, Division of Medical Oncology, University of Kentucky College of Medicine, Lexington, KY, 40536, USA; Markey Cancer Center, Lexington, KY, 40536, USA. Electronic address: ., Markey Cancer Center, Lexington, KY, 40536, USA; Department of Urology, University of Kentucky College of Medicine, Lexington, KY, 40536, USA. Electronic address: ., Department of Pathology and Laboratory Medicine, University of Kentucky College of Medicine, Lexington, KY, 40536, USA; Markey Cancer Center, Lexington, KY, 40536, USA; Department of Urology, University of Kentucky College of Medicine, Lexington, KY, 40536, USA. Electronic address: .