Molecular markers to complement sentinel node status in predicting survival in patients with high-risk locally invasive melanoma.

Sentinel lymph node status is a major prognostic marker in locally invasive cutaneous melanoma. However, this procedure is not always feasible, requires advanced logistics and carries rare but significant morbidity. Previous studies have linked markers of tumour biology to patient survival. In this study, we aimed to combine the predictive value of established biomarkers in addition to clinical parameters as indicators of survival in addition to or instead of sentinel node biopsy in a cohort of high-risk melanoma patients. Patients with locally invasive melanomas undergoing sentinel lymph node biopsy were ascertained and prospectively followed. Information on mortality was validated through the National Death Index. Immunohistochemistry was used to analyse proteins previously reported to be associated with melanoma survival, namely Ki67, p16 and CD163. Evaluation and multivariate analyses according to REMARK criteria were used to generate models to predict disease-free and melanoma-specific survival. A total of 189 patients with available archival material of their primary tumour were analysed. Our study sample was representative of the entire cohort (N = 559). Average Breslow thickness was 2.5 mm. Thirty-two (17%) patients in the study sample died from melanoma during the follow-up period. A prognostic score was developed and was strongly predictive of survival, independent of sentinel node status. The score allowed classification of risk of melanoma death in sentinel node-negative patients. Combining clinicopathological factors and established biomarkers allows prediction of outcome in locally invasive melanoma and might be implemented in addition to or in cases when sentinel node biopsy cannot be performed.

Clinical and biological determinants of melanoma progression: Should all be considered for clinical management?

Cutaneous melanoma is a heterogeneous disease affecting the regulation of multiple genes and proteins that contribute to melanoma progression. Survival for patients with locally invasive disease varies greatly, even within tumour stages based on current prognostic criteria. This has prompted investigations into the value of additional clinical or biological parameters predicting survival. In particular, the improved knowledge of tumour biology has fed the hope that the outcome may be predicted at the molecular level. The prognostic value of numerous potential biomarkers has therefore been evaluated in protein and gene expression studies, and genomic associations with melanoma prognosis are beginning to emerge. These potential biomarkers interrogate key tumour and host processes important for tumour development and progression, such as proliferation, invasion and migration through epithelial mesenchymal transition or the host immune or vascular responses. This research may allow more individualised information on prognosis if the challenges regarding the quality and validation of studies are overcome.

Warfarin-induced erythroderma.

Erythroderma is a potentially serious and life-threatening skin disease with a number of possible aetiologies. Drug reactions are well-documented causes, with carbamazepine, penicillin and allopurinol being the most commonly implicated. This case describes a unique presentation of warfarin-induced erythroderma in a 78-year-old female patient.