TRPS1 Antibody
Description
Introduction
The TRPS1 antibody is a highly sensitive and specific immunohistochemical (IHC) marker for diagnosing breast cancer, particularly triple-negative breast cancer (TNBC). Derived from rabbit monoclonal antibodies, it targets the TRPS1 protein, a transcriptional repressor critical in vertebrate development. Recent studies highlight its utility in distinguishing breast cancer from metastatic lesions and non-breast malignancies, though its expression in other tumor types necessitates cautious interpretation .
Mechanism of Action
TRPS1 (trichorhinophalangeal syndrome type 1) is a zinc finger transcription factor that represses GATA-regulated genes, influencing chondrocyte proliferation and differentiation. The antibody binds specifically to nuclear TRPS1 protein, enabling visualization via IHC. Its role in breast cancer diagnosis stems from its high expression in luminal epithelial cells of breast glands, with minimal or no expression in most non-breast tissues under normal conditions .
Key Function:
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Transcriptional Repression: TRPS1 regulates genes involved in cartilage development and tumor suppression .
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Antibody Specificity: Rabbit monoclonal clones (e.g., EP392, EPR16171) exhibit high batch-to-batch consistency and nuclear staining specificity .
Breast Cancer Subtypes
TRPS1 demonstrates superior sensitivity for TNBC (86–100%) compared to traditional markers like GATA3 (51–21%) and mammaglobin (30%) .
| Breast Cancer Subtype | TRPS1 Positivity (%) | GATA3 Positivity (%) |
|---|---|---|
| ER-positive | 98 | 95 |
| HER2-positive | 87 | 88 |
| Metaplastic TNBC | 86 | 21 |
| Nonmetaplastic TNBC | 86 | 51 |
Non-Breast Tumors
While TRPS1 is highly specific for breast cancer, recent studies reveal positivity in:
| Tumor Type | TRPS1 Positivity (%) |
|---|---|
| Synovial Sarcoma | 96 |
| Salivary Gland Tumors | 46.2 |
| Squamous Cell Carcinoma | 34.7 |
| Urothelial Neoplasms | 1.8 |
Specificity Concerns
TRPS1 expression in non-breast cancers (e.g., prostate adenocarcinoma, endometrial carcinoma) necessitates multi-marker panels to enhance diagnostic accuracy. For example, combining TRPS1 with GATA3 improves specificity for TNBC .
Antibody Clone Variability
Performance varies among clones:
| Clone | Primary Application | Key Feature |
|---|---|---|
| EP392 | TNBC Diagnosis | High sensitivity in metaplastic TNBC |
| EPR16171 | General IHC | Recombinant format for consistency |
| RM518 | Breast Lesion Confirmation | Strong nuclear staining |
TCGA Data Analysis
TCGA studies confirm TRPS1 as a breast-specific gene, with minimal expression in 30 other tumor types. Its expression correlates with tumor aggressiveness in basal-like breast cancers .
Prognostic Utility
Low TRPS1 expression in invasive breast carcinoma correlates with high-grade tumors, suggesting a potential prognostic role .
Product Specs
Target Background
- Mutations in PRKAR1A, PDE4D, TRPS1, and PTHLH have been identified in Pseudohypoparathyroidism. PMID: 29499646
- Two Pakistani families with sequence variants in GDF5 and TRPS1 have been reported, causing brachydactyly type C and tricho-rhino-phalangeal syndrome type III. PMID: 29436063
- Research suggests a prominent role for TRPS1 in the development of subependymoma. PMID: 28528424
- Studies have shown that TRPS1 and GATA3 are distinctly overexpressed in breast cancer (BC) among all GATA family members and predict better survival in patients with BC. This makes TRPS1 a distinctive biomarker and an essential prognostic factor in BC. PMID: 28423734
- Downregulation of the TRPS1 protein, a transcriptional target of hsa-miR-26b-5p, has been linked to radiation exposure. PMID: 28944451
- Two patients with novel heterozygous mutations in the TRPS1 gene have been identified. The first patient has a two-base-pair deletion in exon 6, causing a frameshift and an alternate stop codon. The second patient has a large deletion encompassing both TRPS1 and CSMD3. PMID: 28256045
- A case report described twins with heterozygous mutations in the SACS gene, associated with autosomal recessive spastic ataxia of Charlevoix Saguenay. They also carried a heterozygous mutation in the TRPS1 gene, responsible for Trichorhinophalangeal syndrome type 1A. Additionally, a TBL1XR1 mutation was identified in another patient, contributing to cognitive impairment and autistic features. PMID: 27133561
- Three patients presented with TRPS1, two of whom had multiple supernumerary teeth. A novel TRPS1 mutation confirmed the clinical impression. PMID: 27706911
- Family studies have shown that patients with more pronounced facial characteristics and more severe shortening of hands and feet are more likely to have mutations in exon 6 of TRPS1. PMID: 28468609
- Downregulation of TRPS1 by miR-373, acting as a transcriptional activator, promotes epithelial-mesenchymal transition (EMT) and metastasis by repressing FOXA1 transcription, expanding upon its previously reported role as a transcription repressor. PMID: 26969828
- The TRPS1 gene has been identified as the primary genetic factor responsible for the majority of the TRPS phenotype. PMID: 27826100
- Research indicates that co-silencing of tricho-rhino-phalangeal-syndrome (TRPS1) and cathepsin D (Cath-D) in breast cancer cells affects the transcription of cell cycle and proliferation. PMID: 26183398
- Trps1 plays a critical role in osteosarcoma angiogenesis, metastasis, and clinical surgical stage. PMID: 26377811
- Single nucleotide polymorphisms in the TRPS1 gene have been associated with Coronary Artery Disease. PMID: 25328121
- Missense mutations have been exclusively identified in exons 6 and 7 of TRPS1 in patients with tricho-rhino-phalangeal syndrome. PMID: 25792522
- TRPS1 haploinsufficiency results in STAT3 and SOX9 mRNA expression in Trichorhinophalangeal syndrome. PMID: 25136899
- Trps1 is implicated in the pathogenesis of non-anastomotic biliary structure following liver transplantation and negatively correlates with biliary epithelial cell epithelial-mesenchymal transition and biliary fibrosis in liver grafts. PMID: 25886207
- Studies propose that TRPS1 acts as a central hub in the control of cell cycle and proliferation during cancer development. PMID: 25277197
- A novel missense mutation c.2726G>A (p.C909Y) of the TRPS1 gene has been identified in a family with trichorhinophalangeal syndrome type I. PMID: 25333908
- The truncated protein from the mutant allele may be stably expressed in patient's hair follicles. PMID: 24909213
- A mutation in the TRPS1 gene has been identified. The same mutation was detected as a 10% mosaic mutation by Pyrosequencing in blood-derived DNA from his healthy mother. This is the first time that somatic mosaicism has been identified in TRPSI. PMID: 23572024
- TRPS1 gene expression is associated with different epithelial mesenchymal transformation markers in ERalpha-positive and ERalpha-negative breast cancers. PMID: 24934762
- Trps1 is essential for odontoblast maturation by supporting the expression of genes crucial for initiating the mineralization process. PMID: 25128529
- An association between SNP within TRPS1 and BMD has been observed. PMID: 24416236
- TRPS1 promotes angiogenesis and affects VEGFA expression in breast cancer. PMID: 24595984
- TRPS-1 is an independent prognostic marker in early-stage breast cancer and a new epithelial-to-mesenchymal transition marker that can distinguish patients with estrogen receptor-positive breast cancer who will respond longer to adjuvant endocrine therapy. PMID: 23729783
- A role for Trps1 in the regulation of MDR1 expression in osteosarcoma has been identified. PMID: 24491996
- A new mutation in the TRPS1 gene leading to tricho-rhino-phalangeal syndrome I has been identified in a Chinese patient. PMID: 23293878
- The first familial balanced translocation [t(8;13)(q24.11;q21.31)] leading to trichorhinophalangeal syndrome I with a breakpoint 87 kb from the TRPS1 5' end has been reported. PMID: 23835950
- Increased expression of TRPS1 may be involved in the pathogenesis and progression of colon cancer. PMID: 23762846
- The strong expression of TRPS-1 may serve as a good prognostic marker in breast cancer. PMID: 24074613
- Mutations in the amino terminus of this transcription factor result in TRPS I syndrome. PMID: 22481165
- Genetic variation in TRPS1 may regulate hip geometry as well as bone mineral density. PMID: 22306695
- TRPS1 codon 952 constitutes a mutational hot spot in trichorhinophalangeal syndrome type I and could be associated with intellectual disability. PMID: 22127049
- miR-221/222 targeting of trichorhinophalangeal 1 (TRPS1) promotes epithelial-to-mesenchymal transition in breast cancer. PMID: 21868360
- Significant differences in TRPS-1 expression have been observed in primary breast cancer. PMID: 21761348
- TRPS-1 has been found to be expressed in a high proportion of ER(-) ductal epithelial breast cancers. PMID: 21761336
- TRPS1 targeting by miR-221/222 promotes the epithelial-to-mesenchymal transition in breast cancer. PMID: 21673316
- Nonsense mutations result in premature stop codons in exon 4 or exon 5, and frame shifts from deletions or two-to-one substitutions also lead to premature stop codons downstream. PMID: 20394624
- Mutations in TRPS1 have been linked to tricho-rhino-pharangeal syndrome. PMID: 20635356
- A family study reported a novel out-of-frame indel, the largest intragenic indel reported to date, in a father and three children affected by a mild form of trichorhinophalangeal syndrome type I. The study also commented on the intrafamilial consistency of the resulting TRPS type I phenotype. PMID: 20177376
- A review explored the structure and function of GC79/TRPS1, a novel androgen-repressible apoptosis gene. PMID: 11773701
- Studies have identified novel and recurrent mutations responsible for the tricho-rhino-phalangeal syndromes. PMID: 11950061
- Homologous domains from the TRPS-1 and Drosophila Hunchback proteins support homodimerization but not heterodimerization with Ikaros. PMID: 12620233
- TRPS1 activity is regulated by RNF4. PMID: 12885770
- Research suggests a role for TRPS1 in androgen regulation of prostate-specific antigen gene expression. PMID: 14680804
- TRPS-1 protein and gene were expressed in over 90% of early- and late-stage breast cancer, including ductal carcinoma in situ and invasive ductal, lobular, and papillary carcinomas. PMID: 16043716
- TRPS1 is SUMOylated at multiple sites, both in vivo and in vitro, through interaction with UBC9. Overexpression of wild-type UBC9 enhances TRPS1-mediated transcriptional repression. PMID: 17391059
- A study suggests a possible involvement of TRPS1 in oxidative stress and possibly in apoptosis in androgen-independent DU145 prostate cancer cells. PMID: 17467349
- A study reported a family affected by a mild form of trichorhinophalangeal syndrome type I. Mutation analysis showed a missense mutation (R952C) in exon 7 of the TRPS1 gene. PMID: 17854380
Q&A
How should researchers validate TRPS1 antibody specificity in immunohistochemistry (IHC)?
Validation requires a multi-step approach:
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Knockout Controls: Use TRPS1-knockout cell lines or CRISPR-edited tissues to confirm absence of staining .
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Orthogonal Methods: Compare IHC results with Western blot (WB) or RNA-seq data from the same sample. For example, a Spearman correlation of r = 0.9 (P < 0.001) between TRPS1 mRNA and protein levels was observed in colon cancer .
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Cross-Reactivity Testing: Assess reactivity against homologous proteins (e.g., GATA3) using peptide blocking assays. Antibodies like ab125197 show minimal cross-reactivity due to immunogen design targeting residues 1000–1050 .
What are the primary experimental applications of TRPS1 antibodies?
TRPS1 antibodies are utilized in:
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Diagnostic IHC: Discriminating breast carcinomas (86% sensitivity) from urothelial neoplasms (1.8% positivity) .
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Co-Expression Studies: Pairing with GATA3 to identify dual-positive tumors (47.4–100% in breast cancer vs. 0.3% in non-mammary malignancies) .
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Mechanistic WB: Detecting TRPS1’s 141.5 kDa band in nuclear extracts, as validated in prostate and breast cancer cell lines .
How does TRPS1 expression differ between normal and malignant tissues?
TRPS1 is expressed in normal prostate, kidney, and mammary glands but upregulated in malignancies:
How can contradictions in TRPS1 expression data across studies be resolved?
Discrepancies often arise from:
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Antibody Clonal Variability: Clone EPR16171 shows nuclear-specific staining, while PA-84874 exhibits cytoplasmic artifacts in smooth muscle and lymphocytes .
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Tumor Heterogeneity: Subtyping impacts results; e.g., TRPS1 is negative in basal-like breast cancers but positive in luminal subtypes .
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Quantitative Thresholds: Define “positive” staining using H-scores (e.g., IRS >4.5 correlates with colon cancer progression) .
What mechanistic role does TRPS1 play in cancer metastasis?
TRPS1 promotes metastasis via:
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Transcriptional Repression: Silencing GATA-regulated genes (e.g., CDH1) to enhance epithelial-mesenchymal transition (EMT) .
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Chondrocyte Regulation: In osteosarcoma, TRPS1 activates SOX9 to drive invasiveness .
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Prognostic Value: High TRPS1 in colon cancer associates with advanced pathological stage (HR = 2.1, P = 0.008) .
How does TRPS1 compare to GATA3 as a lineage marker in differential diagnosis?
| Feature | TRPS1 | GATA3 |
|---|---|---|
| Breast Cancer | 51–100% | 70–90% |
| Urothelial Cancer | 1.8% | 45–60% |
| Salivary Gland | ≤46.2% | ≤15% |
| Specificity | Higher in mesenchymal tumors | Limited to epithelial origins |
Dual staining reduces false positives; only 0.3% of non-breast tumors express both markers .
What emerging applications exist for TRPS1 antibodies?
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Single-Cell Sequencing Validation: Confirm TRPS1 mRNA-protein concordance in rare cell populations (e.g., circulating tumor cells).
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Therapeutic Targeting: TRPS1 knockdown via siRNA reduces colon cancer xenograft growth by 40% (P < 0.01) .
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Stromal Interactions: Detect TRPS1 in cancer-associated fibroblasts (CAFs) to assess desmoplastic response .
