Biomolecular markers in head and neck cancer

University dissertation from Uppsala : Acta Universitatis Upsaliensis

Abstract: Head and neck cancer is a heterogeneous group of tumours, of which certain subgroups such as cancer of the mobile tongue frequently are associated with a relatively poor prognosis due to the high risk of regional failure and mortality rates that haven’t improved in a significant way over the last 3 decades, despite advancements in both diagnostics and treatment.Today we lack means to assess the biological aggressiveness of each individual tumour, which varies largely. Treatment comprises of surgery with additional radiotherapy and medical therapies in more advanced tumours.The focus in this thesis is on molecular biomarker expression in head and neck cancer and especially in association with radiotherapy. Increased knowledge paves the way to a more individualized cancer treatment aiming for better outcome and less overtreatment and sequelae.The aims of this thesis was:To map the effects of radiotherapy in both tumour and adjacent tissue for the possible markers hyaluronan, EGFR and mast cells.To investigate whether the expression of hyaluronan in the epithelium and connective tissue stroma and EGFR in the tumour correlates with the risk for developing cervical metastasis in N0 patients, and to find out whether the 3-year tumour-specific survival rates correlates with the expression of HA in the epithelium and EGFR in the tumour.To establish an animal model for radiation-induced mucositis and to use that model to examine the pattern of invading inflammatory cells.To investigate whether the expression of podoplanin in tongue cancer correlates with the risk for cervical metastasis and to determine whether the total amount of lymph vessels in the diagnostic biopsy has any impact on the clinical outcome.To investigate the differences in the metabolome of tongue cancer cell lines with different radiosensitivity.The most important findings of this thesis were:The expression of EGFR and hyaluronan hade the same pattern of expression in both tumour and adjacent tissues before radiotherapy. The expression of EGFR was increased in the epithelium of the adjacent tissue close to the tumour after radiotherapy.The intensity of the staining of hyaluronan was correlated to the 3-year survival rates in patients with tongue cancer.An experimental model for radiation-induced oral mucositis in rat was established and in this model a temporal pattern of macrophage invasion with two different subtypes of macrophages was found.There were no correlation between the expression of podoplanin in the tumour tissue and the cervical metastasis rate in patients with tongue cancer, but the younger patients were more likely to have a higher expression of podoplanin in their tumour than elder patients.Tongue cancer cell lines with different radiosensitivity respond to irradiation with different patterns of metabolic expressions.