Clinical associations and prognostic significance of mitotic rate in primary cutaneous melanoma

Melanoma is a significant cause of morbidity and mortality in Australia. Whilst recent developments in targeted therapies have offered exciting breakthroughs in the treatment of advanced disease, survival rate remains grim for those afflicted with the systemic spread of melanoma. For local cutaneous disease, a patient’s initial prognosis is primarily determined by the stage which the melanoma is first diagnosed, reflected largely but not solely by its Breslow thickness. Attempts are being made to better understand both the clinical and histologic heterogeneity of melanoma, since it is recognized that some subtypes of melanoma behave more aggressively than others. This thesis aims to examine the distinct clinical and histopathologic features of aggressive primary cutaneous melanomas, as a means to aid clinicians with timely detection of at-risk individuals. It also aims to extend upon our current knowledge of melanoma prognostication. In order to pursue these aims, two original studies were undertaken; both focused on mitotic rate, a histologic feature used to quantify the degree of tumour cell proliferation and has emerged in recent years as an important prognosticator of clinical outcomes. The first study of this thesis seeks to elucidate patient and tumour characteristics associated with mitotically active melanoma. The predictive value of mitotic rate for melanoma survival was explored in the second study.