p63 isoforms in triple-negative breast cancer: ΔNp63 associates with the basal phenotype whereas TAp63 associates with androgen receptor, lack of BRCA mutation, PTEN and improved survival
Jazyk angličtina Země Německo Médium print-electronic
Typ dokumentu časopisecké články
PubMed
29484502
DOI
10.1007/s00428-018-2324-2
PII: 10.1007/s00428-018-2324-2
Knihovny.cz E-zdroje
- Klíčová slova
- Androgen receptor, BRCA1, BRCA2, PTEN, TAp63, Triple-negative breast cancer, ΔNp63,
- MeSH
- fenotyp MeSH
- fosfohydroláza PTEN genetika MeSH
- lidé MeSH
- lokální recidiva nádoru genetika MeSH
- mutace genetika MeSH
- nádorové supresorové proteiny genetika MeSH
- protein - isoformy genetika MeSH
- protein BRCA1 genetika MeSH
- protein BRCA2 genetika MeSH
- regulace genové exprese u nádorů genetika MeSH
- transkripční faktory genetika MeSH
- triple-negativní karcinom prsu genetika metabolismus mortalita MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- BRCA1 protein, human MeSH Prohlížeč
- BRCA2 protein, human MeSH Prohlížeč
- fosfohydroláza PTEN MeSH
- nádorové supresorové proteiny MeSH
- protein - isoformy MeSH
- protein BRCA1 MeSH
- protein BRCA2 MeSH
- PTEN protein, human MeSH Prohlížeč
- TP63 protein, human MeSH Prohlížeč
- transkripční faktory MeSH
The TP63 gene encodes two major protein variants that differ in their N-terminal sequences and have opposing effects. In breast, ΔNp63 is expressed by immature stem/progenitor cells and mature myoepithelial/basal cells and is a characteristic feature of basal-like triple-negative breast cancers (TNBCs). The expression and potential role of TAp63 in the mammary gland and breast cancers is less clear, partly due to the lack of studies that employ p63 isoform-specific antibodies. We used immunohistochemistry with ΔNp63-specific or TAp63-specific monoclonal antibodies to investigate p63 isoforms in 236 TNBCs. TAp63, but not ΔNp63, was seen in tumour-associated lymphocytes and other stromal cells. Tumour cells showed nuclear staining for ΔNp63 in 17% of TNBCs compared to 7.3% that were positive for TAp63. Whilst most TAp63+ tumours also contained ΔNp63+ cells, the levels of the two isoforms were independent of each other. ΔNp63 associated with metaplastic and medullary cancers, and with a basal phenotype, whereas TAp63 associated with androgen receptor, BRCA1/2 wild-type status and PTEN positivity. Despite the proposed effects of p63 on proliferation, Ki67 did not correlate with either p63 isoform, nor did they associate with p53 mutation status. ΔNp63 showed no association with patient outcomes, whereas TAp63+ patients showed fewer recurrences and improved overall survival. These findings indicate that both major p63 protein isoforms are expressed in TNBCs with different tumour characteristics, indicating distinct functional activities of p63 variants in breast cancer. Analysis of individual p63 isoforms provides additional information into TNBC biology, with TAp63 expression indicating improved prognosis.
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