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Updated: Jul 5, 2025
Establishment of a Clinic-based Biorepository
Published on: May 29, 2017
A Sub-Group of Kidney-Transplant Recipients with Highly Aggressive Squamous Cell Carcinoma Expressing Phosphorylated
Diaddin Hamdan1,2, Charlotte Gardair1, Frédéric Pamoukdjian1,3,4
1Faculté de Santé, Site Lariboisière, Institut National de la Santé et de la Recherche Médicale INSERM, Unité Mixte de Recherche UMR_S942 MASCOT, Université Paris-Cité, F-75006 Paris, France.
Abstract:
Cutaneous squamous cell carcinomas in kidney-transplant recipients are frequent, with an increasing incidence linked to long immunosuppression durations and exposure to ultraviolet radiation. p53 is at the cornerstone of ultraviolet-induced DNA damage, but the role of p53 post-translational modifications in this context is not yet deciphered. Here, we investigated the phosphorylation status of p53 at Serine 392 in 25 cutaneous squamous cell carcinomas in kidney-transplant recipients, compared with 22 non-transplanted patients. Cutaneous squamous cell carcinomas in transplanted patients occurred after a median period of 19 years of immunosuppression, with a median number of 15 cutaneous squamous cell carcinomas and more aggressive histological and clinical characteristics. There was no significant difference between Ki67, p53, and pSer392p53 expression in the two groups. Using principal component analysis, we identified a cluster of exclusively transplanted patients with a median of 23 years of immunosuppression duration, significantly more aggressive biological characteristics, and higher pSer392p53 expression. pSer392p53 was expressed in the whole tumor, suggesting an early carcinogenic event in the course of prolonged immunosuppression. This high, diffuse pSer392p53 expression, corresponding to a high level of DNA damage, might be useful to identify aggressive cutaneous squamous cell carcinomas in kidney-transplant recipients to treat them more aggressively.
Insights
Kidney transplant recipients with prolonged immunosuppression show increased risk of aggressive skin cancers. Higher p53 Serine 392 phosphorylation (pSer392p53) in tumors may indicate early carcinogenic events and aggressive disease.
Area of Science:
- Oncology
- Immunology
- Dermatology
Background:
- Cutaneous squamous cell carcinomas (cSCC) are common in kidney transplant recipients (KTRs).
- Long-term immunosuppression and UV exposure increase cSCC incidence in KTRs.
- The role of p53 post-translational modifications in UV-induced DNA damage and cSCC in KTRs is unclear.
Purpose of the Study:
- To investigate the phosphorylation status of p53 at Serine 392 (pSer392p53) in cSCC from KTRs.
- To compare pSer392p53 expression in cSCC between KTRs and non-transplanted patients.
- To correlate pSer392p53 expression with clinical and histological characteristics of cSCC in KTRs.
Main Methods:
- Analysis of p53 phosphorylation at Serine 392 in 25 cSCC from KTRs and 22 non-transplanted patients.
- Comparison of Ki67, p53, and pSer392p53 expression between groups.
- Principal component analysis (PCA) to identify patient clusters based on immunosuppression duration and tumor characteristics.
Main Results:
- No significant difference in Ki67, p53, or pSer392p53 expression between KTRs and non-transplanted patients overall.
- PCA identified a cluster of KTRs with longer immunosuppression (median 23 years), more aggressive characteristics, and higher pSer392p53 expression.
- Diffuse pSer392p53 expression in tumors suggests an early event in prolonged immunosuppression and correlates with DNA damage.
Conclusions:
- High, diffuse pSer392p53 expression may identify aggressive cSCC in KTRs.
- pSer392p53 could serve as a biomarker for aggressive cSCC in KTRs, potentially guiding more intensive treatment.
- Further research is needed to elucidate the precise role of p53 modifications in cSCC pathogenesis in immunosuppressed patients.
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