Altered endosomal-lysosomal biogenesis in melanoma.

Cutaneous melanoma is the deadliest form of skin neoplasm and its high mortality rates could be averted by early accurate detection. While the detection of melanoma is currently reliant upon melanin visualisation, research into melanosome biogenesis, as a key driver of pathogenesis, has not yielded technology that can reliably distinguish between atypical benign, amelanotic and melanotic lesions. The endosomal-lysosomal system has important regulatory roles in cancer cell biology, including a specific functional role in melanosome biogenesis. Herein, the involvement of the endosomal-lysosomal system in melanoma was examined by pooled secondary analysis of existing gene expression datasets. A set of differentially expressed endosomal-lysosomal genes was identified in melanoma, which were interconnected by biological function. To illustrate the protein expression of the dysregulated genes, immunohistochemistry was performed on samples from patients with cutaneous melanoma to reveal candidate markers. This study demonstrated the dysregulation of Syntenin-1, Sortilin and Rab25 may provide a differentiating feature between cutaneous melanoma and squamous cell carcinoma, while IGF2R may indicate malignant propensity in these skin cancers.

Are cutaneous melanomas of specified thickness showing deeper levels of invasion at diagnosis?

Secular trends in Clark level were investigated by Breslow category for 8,432 invasive cutaneous melanomas diagnosed in South Australia in 1980-2000. More recently diagnosed lesions were found to have deeper levels. After adjusting for age at diagnosis, tumour site, histology, and thickness measured in half millimetres, the relative odds (95% confidence limits) of penetration to the reticular dermis or subcutaneous fat were 1.99 (1.59, 2.50) for the 1987-93 diagnostic period, and 2.82 (2.25, 3.54) for 1994-2000, when compared with 1980-86. After adjusting for melanoma thickness, the secular trends for deeper lesions applied to a broad cross-section of socio-demographic sub-groups, tumour sites, and histological types. While this similarity in trend would be consistent with a measurement effect, a real change cannot be ruled out and increased emphasis on earlier detection may be warranted. The prognostic implications of changes in inter-relationships between measures of thickness and level require periodic re-evaluation.