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Identification of molecular and immuno diagnostic cancer markers in Northern Territory population

Singh, Jagtar (2013). Identification of molecular and immuno diagnostic cancer markers in Northern Territory population. Master Thesis, Charles Darwin University.

Document type: Thesis
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Author Singh, Jagtar
Title Identification of molecular and immuno diagnostic cancer markers in Northern Territory population
Institution Charles Darwin University
Publication Date 2013
Thesis Type Master
Subjects 1112 - Oncology and Carcinogenesis
1199 - Other Medical and Health Sciences
Abstract Tumour suppressor gene p53 function is impaired in a very large proportion of human cancers, particularly in head and neck squamous cell carcinoma (HNSCC). Overexpression of p53 in the histologically tumour free surgical margins often correlates with a high recurrence rate. The overexpression of p53 observed 50-60% on HNSCC tumours. The eukaryotic translation initiation factor 4E (eIF4E) is overexpressed in 100% of HNSCC.

The study was planned to assess the expression of cancer markers p53 and 4E in histologically tumour negative margins in patients with HNSCC. The intent was to co-relate such expression with clinical evidence of residual or recurrent disease. Our hypothesis was that since cancer is not a uniform and systematical disease, the one-centimeter margin employed by surgeons in their removal could contribute to residual disease. Further, as the pathological investigation requires a minimum number of tumour cells in any given field to detect the cancer in a routine H&E stain, we hypothesized that small islands of tumour could be missed, which would be highlighted with IHC.

A retrospective study was performed on 24 patients who underwent surgery for HNSCC. Total 77 Paraffin-embedded sections from the surgical margins were immunostained with antibodies to 4E and p53. Patient characteristics and surgical margins were analysed. Twenty-one patients (87.5%) showed overexpression of 4E in the surgical margins, whereas 13 patients (54.2%) were p53 positive. In our study, six out of the seven recurrent patients have 4E positive margins, whereas only three patients had recurrence with p53 positive margins. Hence, both p53 and 4E expression in the surgical margins were not significant predictors of cancer recurrence (P = 0.8794, P = 0.9995). Overexpression of 4E found in the margins of 6 out of 7 patients with local recurrence. It was also found that in three patients who had a recurrence with p53 positive.

Molecular studies of the surgical margin could help to identify patients at increased local recurrence risk who have histopathologically clear surgical margins. It can also help to dictate appropriate adjunctive treatments for HNSCC patients. It appears to be logical and feasible that rapid testing will inform the surgical team if their resection is adequate, and permit further guided excision at problematic margins. The absence of overexpression may also benefit the patient in terms of avoiding unnecessary further surgery.


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