Expression profiling of cutaneous squamous cell carcinoma with perineural invasion implicates the p53 pathway in the process.
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.
Department of Otolaryngology, Head and Neck Surgery and Queensland Skull Base Unit, Princess Alexandra Hospital, Brisbane, Queensland, Australia.|School of Medicine, University of Queensland, Brisbane, Queensland, Australia.|Cancer Drug Mechanisms/Drug Discovery Groups, Department of Cell and Molecular Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Timothy A
TA
Warren
Cancer Drug Mechanisms/Drug Discovery Groups, Department of Cell and Molecular Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Natasa
N
Broit
Cancer Drug Mechanisms/Drug Discovery Groups, Department of Cell and Molecular Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Jacinta L
JL
Simmons
Cancer Drug Mechanisms/Drug Discovery Groups, Department of Cell and Molecular Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Carly J
CJ
Pierce
Department of Otolaryngology, Head and Neck Surgery and Queensland Skull Base Unit, Princess Alexandra Hospital, Brisbane, Queensland, Australia.|School of Medicine, University of Queensland, Brisbane, Queensland, Australia.|Cancer Drug Mechanisms/Drug Discovery Groups, Department of Cell and Molecular Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Sharad
S
Chawla
Department of Pathology, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
Duncan L J
DL
Lambie
Sullivan Nicolaides Pathology, Brisbane, Queensland, Australia.
Gary
G
Quagliotto
Envoi Pathology, Brisbane, Queensland, Australia.
Ian S
IS
Brown
Cancer Drug Mechanisms/Drug Discovery Groups, Department of Cell and Molecular Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Peter G
PG
Parsons
Department of Otolaryngology, Head and Neck Surgery and Queensland Skull Base Unit, Princess Alexandra Hospital, Brisbane, Queensland, Australia.|School of Medicine, University of Queensland, Brisbane, Queensland, Australia.
Benedict J
BJ
Panizza
Cancer Drug Mechanisms/Drug Discovery Groups, Department of Cell and Molecular Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Glen M
GM
Boyle
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