- Title
- It is not all about the alpha: elevated expression of p53β variants is associated with lower probability of survival in a retrospective melanoma cohort
- Creator
- Groen, Kira; Steffens Reinhardt, Luiza; Bourdon, Jean-Christophe; Avery-Kiejda, Kelly A.
- Relation
- Cancer Cell International Vol. 23, Issue 1, no. 228
- Publisher Link
- http://dx.doi.org/10.1186/s12935-023-03083-6
- Publisher
- BioMed Central
- Resource Type
- journal article
- Date
- 2023
- Description
- Background: Melanoma is the deadliest type of skin cancer and despite improvements in treatment outcomes, melanoma claimed 57,043 lives in 2020. In most malignancies, p53 mutation rates are above 50% and provide prognostic indications. However, in melanoma where less than a quarter of cases harbour a p53 mutation, the significance of the tumour suppressor may be questioned. Instead, p53 isoforms, which modulate p53's canonical function, may be of greater clinical importance. Methods: The expression of p53 isoforms was evaluated in 123 melanoma specimens by immunohistochemistry using p53 isoform-specific antibodies (DO-1, KJC8, KJC40, and KJC133). To determine whether TP53 mutations may be driving p53 isoform expression, TP53 was sequenced in 30 FFPE melanoma samples. Results: The C-terminally truncated p53β isoforms (KJC8) were found to be the most highly expressed p53 isoforms compared to all other isoforms. Further, elevated KJC8 staining was found to correlate with reduced probability of melanoma-specific survival, while KJC40 staining (Δ40p53) positively correlated with reduced melanoma thickness. TAp53 isoforms (p53 retaining both transactivation domains, DO-1), were the second highest p53 isoforms expressed across all samples. Elevated DO-1 staining was also associated with worse survival outcomes and more advanced stages of cancer. Given that the isoforms are likely to work in concert, composite isoform profiles were generated. Composite biomarker profiles revealed that elevated TAp53 (DO-1) and p53β (KJC8) expression, accompanied by low Δ40p53 (KJC40) and Δ133p53 (KJC133) expression was associated with the worst survival outcomes. Supporting the lack of predictive biomarker potential of TP53 in melanoma, no clinicopathological or p53 isoform expression associations could be linked to TP53 status. Conclusions: Given the lack of prognostic biomarker potential derived from TP53 status, this study highlights how p53 isoform expression might progress this field and, pending further validation, may provide additional information to treating oncologists that might be factored into treatment decisions.
- Subject
- p53 isoforms; melanoma; immunohistochemistry; biomarker; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1492505
- Identifier
- uon:53356
- Identifier
- ISSN:1475-2867
- Rights
- © 2023 The Author(s). This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
- Language
- eng
- Full Text
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