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?

Abstract

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.

Keywords: Breast carcinoma; GATA3; Immunohistochemistry; Prostate carcinoma; TRPS1; Triple-negative breast carcinoma; Urothelial carcinoma.

Figure 1

A-B. GISTIC analysis revealing frequency of TRPS1 gene alterations across multiple cancer types

Figure 2.

Prostate cancer outcomes for patients with TRPS1 gene alterations. A-D) In prostate cancer, patients with an altered TRPS1 gene had a statistically significant worse progression free (A), disease free (B), disease-specific (C), and overall survival (D) when compared to those with an unaltered gene in the TCGA Cohort.

Figure 3:

TRPS1 mRNA Expression in Prostate and Bladder Cancer. A) TRPS1 mRNA across Gleason scores in 296 prostate cancer and 52 normal samples in the TCGA Cohort. Although the highest expression is seeing in Gleason Score 10, note the small sample size and the largely uniform expression level. B) mRNA expression of TRPS1 in 406 bladder cancer samples from the TCGA cohort revealing high expression is correlated with a worse overall survival.

Figure 4.

TRPS1 and GATA3 Immunohistochemical Expression in Bladder Urothelial Carcinoma. A, B, C) Urothelial carcinoma showing a lack of TRSP1 and high GATA3 expression, H&E stain, TRPS1 stain, and GATA3 stain, respectively, 20x magnification. D, E, F) Urothelial carcinoma showing intermediate TRPS1 expression and high GATA3 expression, H&E stain, TRPS1 stain, and GATA3 stain, respectively, 40x magnification. G, H, I) Urothelial carcinoma showing high TRPS1 expression and high GATA3 expression, H&E stain, TRPS1 stain, and GATA3 stain, respectively, 40x magnification.

Figure 5.

TRPS1 and GATA3 Immunohistochemical Expression in Prostate Cancer. A, B, C) Prostate cancer showing a lack of TRSP1 and GATA3 expression, H&E stain, TRPS1 stain, and GATA3 stain, respectively, 40x magnification. D, E, F) Prostate cancer showing intermediate TRPS1 expression and a lack of GATA3 expression, H&E stain, TRPS1 stain, and GATA3 stain, respectively, 40x magnification. G, H, I) Prostate cancer showing high TRPS1 expression and a lack of GATA3 expression, H&E stain, TRPS1 stain, and GATA3 stain, respectively, 40x magnification.

Figure 6.

TRPS1 and GATA3 Immunohistochemical Expression in a Triple Negative Breast Cancer Case. A, B, C) Triple negative breast carcinoma showing high TRPS1 expression and a lack of GATA3 expression, H&E stain, TRPS1 stain, and GATA3 stain, respectively, 20x magnification.