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• W2780580329 abstract "The invasion and spread of cutaneous squamous cell carcinoma of the head and neck (CSCCHN) along nerves is an aggressive metastatic form of an otherwise treatable condition. Following initial perineural invasion (PNI) of a peripheral nerve, tumour cells can spread along cranial and spinal nerves away from the site of the primary skin cancer. Queensland, Australia has high recorded rates of skin cancer and this advanced form of the disease can be associated with poor prognosis.Skin cancer with PNI detected only on histology in an asymptomatic patient is termed incidental PNI. When there is spread of tumour along the nerve evidenced either clinically with symptoms and signs of nerve involvement and/or radiologically this is termed clinical PNI or perineural spread (PNS). Awareness of perineural disease amongst clinicians and patients is limited and analysis of the disease epidemiology and natural history is required. The molecular factors involved in the invasion and spread of tumour cells along nerves remain unknown.This thesis aimed to assess and define the epidemiology and natural history including treatment outcomes of CSCCHN with PNS. In addition, molecular analysis through whole genome expression profiling with targeted functional analysis of potentially significant genes was undertaken. The primary aim of this work was to contribute to the awareness and understanding of this disease process to improve patient management and outcomes. This thesis has described specific epidemiological features of patients with this disease. The important findings were that patients can present with PNS of CSCCHN without a known primary tumour, and that the initial primary tumour may not necessarily have had PNI detected. In addition, the majority of patients did not have regional nodal involvement at presentation. A clinical profile including common symptoms and signs and the timeline to diagnosis was also defined. Treatment with surgery and post-operative radiotherapy can offer reasonable outcomes with limited complications. Genomic expression profiling demonstrated 6917 genes between CSCCHN, CSSCHN with incidental PNI and CSCCHN with clinical PNI that were differentially expressed. Analysis suggests that multiple pathways may be involved in the pathogenesis. LOXL2 was demonstrated to be a gene of interest and was validated on immunohistochemistry. LOXL2 was both over-expressed and silenced through gene transfection in various epithelial cell lines. Functional analysis did not demonstrate any changes in the neoplastic properties of the cell lines with LOXL2 over-expression and silencing.This thesis has contributed significantly to the understanding of the disease process at both a clinical and molecular level. Several findings detailed in this body of work have not previously been described. This will ideally raise awareness of this rare disease and guide clinicians in its assessment and treatment to culminate in an improvement in patient outcomes." @default.
• W2780580329 created "2018-01-05" @default.
• W2780580329 creator A5047721763 @default.
• W2780580329 date "2017-12-20" @default.
• W2780580329 modified "2023-09-27" @default.
• W2780580329 title "Epidemiological and molecular features of cutaneous squamous cell carcinoma with perineural spread" @default.
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