TRPS1 is a Highly Sensitive Marker for Breast Cancer: A Tissue Microarray Study Evaluating More Than 19,000 Tumors From 152 Different Tumor Entities

Abstract

Trichorhinophalangeal syndrome 1 (TRPS1) is a nuclear protein highly expressed in breast epithelial cells. TRPS1 immunohistochemistry (IHC) has been suggested as a breast cancer marker. To determine the diagnostic and prognostic utility of TRPS1 IHC, tissue microarrays containing 19,201 samples from 152 different tumor types and subtypes were analyzed. GATA3 IHC was performed in a previous study. TRPS1 staining was seen in 86 of 152 tumor categories with 36 containing at least one strongly positive case. TRPS1 staining predominated in various types of breast carcinomas (51%-100%), soft tissue tumors (up to 100%), salivary gland tumors (up to 46%), squamous cell carcinomas (up to 35%), and gynecological cancers (up to 40%). TRPS1 positivity occurred in 1.8% of 1083 urothelial neoplasms. In invasive breast carcinoma of no special type, low TRPS1 expression was linked to high grade ( P = 0.0547), high pT ( P < 0.0001), nodal metastasis ( P = 0.0571), loss of estrogen receptor and progesterone receptor expression ( P < 0.0001 each), and triple-negative status ( P < 0.0001) but was unrelated to patient survival ( P = 0.8016). In squamous cell carcinomas from 11 different sites, low TRPS1 expression was unrelated to tumor phenotype. Positivity for both TRPS1 and GATA3 occurred in 47.4% to 100% of breast cancers, up to 30% of salivary gland tumors, and 29 (0.3%) of 9835 tumors from 134 other cancer entities. TRPS1 IHC has high utility for the identification of cancers of breast (or salivary gland) origin, especially in combination with GATA3. The virtual absence of TRPS1 positivity in urothelial neoplasms is useful for the distinction of GATA3-positive urothelial carcinoma from breast cancer.

FIGURE 1

TRPS1 immunostaining of normal tissues. The panels show a strong nuclear staining of breast epithelial cells (A) epithelial cells of the endometrium (B), and glial cells in the brain (C). Variable nuclear staining also occurred in suprabasal cells of esophageal squamous epithelium (D), sebaceous glands of the skin (E), epithelial cells of the fallopian tube (F), atrophic epithelial cells of the prostate (G), some tubular cells of the kidney (H), spermatogonia of the testis (I), epithelial cells of the gallbladder (J), smooth muscle cells of the appendix (K), and amnion cells (L).

FIGURE 2

TRPS1 immunostaining in cancer. The panels show a nuclear TRPS1 positivity of variable intensity in an invasive breast carcinoma of no special type (A) a lobular breast carcinoma (B), an adenoid cystic carcinoma of the parotid gland (C), a synovial sarcoma (D), a squamous cell carcinoma of oral cavity (E), a high-grade serous carcinoma of the ovary (F), and a recurrent adenocarcinoma of the prostate (G). TRPS1 staining is lacking in urothelial carcinoma of the urinary bladder (H).

FIGURE 3

Ranking order of TRPS1 immunostaining in tumors. Both the percentage of positive cases (blue dots) and the percentage of strongly positive cases (orange dots) are shown.

FIGURE 4

TRPS1 and GATA3 immunostaining in tumors.

FIGURE 5

Comparison with previous TRPS1 literature. An “X” indicates the fraction of TRPS1-positive tumors in the present study, and dots indicate the reported frequencies from the literature for comparison; red dots mark studies with <100 analyzed tumors and yellow dots mark studies with ≥100 analyzed tumors.