Related Experiment Video
Updated: Mar 14, 2026
Establishment of a Clinic-based Biorepository
Published on: May 29, 2017
Expression profiling of cutaneous squamous cell carcinoma with perineural invasion implicates the p53 pathway in the
Timothy A Warren1,2,3, Natasa Broit3, Jacinta L Simmons3
1Department of Otolaryngology, Head and Neck Surgery and Queensland Skull Base Unit, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
Abstract:
Squamous cell carcinoma (SCC) is the second most common cancer worldwide and accounts for approximately 30% of all keratinocyte cancers. The vast majority of cutaneous SCCs of the head and neck (cSCCHN) are readily curable with surgery and/or radiotherapy unless high-risk features are present. Perineural invasion (PNI) is recognized as one of these high-risk features. The molecular changes during clinical PNI in cSCCHN have not been previously investigated. In this study, we assessed the global gene expression differences between cSCCHN with or without incidental or clinical PNI. The results of the analysis showed signatures of gene expression representative of activation of p53 in tumors with PNI compared to tumors without, amongst other alterations. Immunohistochemical staining of p53 showed cSCCHN with clinical PNI to be more likely to exhibit a diffuse over-expression pattern, with no tumors showing normal p53 staining. DNA sequencing of cSCCHN samples with clinical PNI showed no difference in mutation number or position with samples without PNI, however a significant difference was observed in regulators of p53 degradation, stability and activity. Our results therefore suggest that cSCCHN with clinical PNI may be more likely to contain alterations in the p53 pathway, compared to cSCCHN without PNI.
Insights
Squamous cell carcinoma with perineural invasion (PNI) shows distinct molecular changes, particularly in the p53 pathway. These findings suggest PNI in head and neck cancers may involve alterations in p53 regulators.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Squamous cell carcinoma (SCC) is a prevalent cancer, with head and neck SCC (cSCCHN) often curable unless high-risk features like perineural invasion (PNI) are present.
- PNI is a critical prognostic factor in cSCCHN, but the underlying molecular mechanisms remain largely unexplored.
Purpose of the Study:
- To investigate the molecular differences in cSCCHN associated with PNI.
- To identify gene expression signatures and pathway alterations in tumors exhibiting PNI.
Main Methods:
- Global gene expression profiling of cSCCHN with and without PNI.
- Immunohistochemical staining for p53 expression.
- DNA sequencing of cSCCHN samples to analyze p53 pathway regulators.
Main Results:
- Gene expression analysis revealed signatures indicative of p53 pathway activation in tumors with PNI.
- Immunohistochemistry showed a higher likelihood of diffuse p53 over-expression in cSCCHN with clinical PNI.
- While mutation number/position in p53 did not differ, regulators of p53 degradation, stability, and activity were significantly altered in PNI-positive tumors.
Conclusions:
- cSCCHN with clinical PNI exhibits distinct molecular alterations compared to tumors without PNI.
- The p53 pathway, including its regulators, appears to be significantly involved in the development or progression of PNI in cSCCHN.
