The cell cycle-related genes AURKA and FOXM1 are overexpressed in melanoma. We show here that AURKA overexpression is associated with poor prognosis in three independent cohorts of melanoma patients and correlates with the presence of genomic amplification of AURKA locus and BRAF mutation. AURKA overexpression may also be driven by increased promoter activation through elements such as ETS and FOXM1 found within the 5' proximal promoter region. Activated MAPK/ERK signaling pathway mediates robust AURKA promoter activation, thereby knockdown of BRAF and ERK inhibition results in reduced AURKA transcription and expression. We show a positive correlation between FOXM1 and AURKA expression in three independent cohorts of melanoma patients. FOXM1 silencing decreases expression of AURKA and late cell cycle genes in melanoma cells. We further found that FOXM1 expression levels are significantly higher in tumors carrying the BRAF mutation compared with the wild-type BRAF (BRAF). Accordingly, the knockdown of BRAF also reduces the expression of FOXM1 in BRAF cells. Moreover, Aurora kinase A and FOXM1 inhibition by either genetic knockdown or pharmacologic inhibitors impair melanoma growth and survival both in culture and in vivo, underscoring their therapeutic value for melanoma patients who fail to benefit from BRAF/MEK signaling inhibition.

877 6 Jones EW, Heyl T. Naevus sebaceus. A report of 140 cases with special regard to the development of secondary malignant tumours. Br J Dermatol 1970; 82: 99-117. 7 Domingo J, Helwig EB. Malign neoplasms associated with nevus sebaceus of Jadassohn. J Am Acad Dermatol 1979; 1: 545-556. 8 Tarkhan II, Domingo J. Metastasizing eccrine porocarcinoma developing in a sebaceous nevus of Jadassohn. Report of a case. Arch Dermatol 1985; 121: 413-415. 9 Yeatman JM, Kilkenny M, Marks R. The prevalance of seborrheic keratoses in an Australian population: does exposure to sunlight play a part in their frequency? Br J Dermatol 1997; 137: 411-414. 10 Misago N, Satoh T, Narisawa Y. Basal cell carcinoma with tricholemmal (at the lower portion) differantiation within seborrheic keratosis.

Calciphylaxis is an uncommon disease characterized by calcification of dermal vessels that determines skin necrosis. Calciphylaxis has been almost exclusively reported in association with renal failure and altered phosphor-calcium metabolism. Only a few cases have been described in hyperparathyroidism, malignancies, and, recently, cirrhosis. We report a patient that developed calciphylaxis related to end-stage alcoholic cirrhosis, without any alteration in the phosphocalcic and parathyroid hormone metabolisms. Possible contributing factors were repeated albumin infusions and low levels of protein C and S.

The incidence of melanoma has been increasing worldwide during recent decades. The objective of the study was to analyse the trends in incidence for in situ and invasive melanoma in the Spanish region of Catalonia during the period of 2008–2017. We designed a cross-sectional study with an age-period-cohort analysis of melanoma patient data from the Network of Melanoma Centres in Catalonia. Our database covered a population of over seven million and included a total of 8626 patients with incident melanoma. The main outcome measures were crude and age-standardised incidence rates to the European 2013 standard population. Joinpoint regression models were used to evaluate the population trends. We observed an increase in the age-standardised incidence rate (per 100,000 population) of all melanoma subtypes from 11.56 in 2008 to 13.78 in 2017 with an average annual percent change (AAPC) of 3.5%. This incidence increase was seen exclusively in the older population. Moreover, the stratified analysis showed a statistically significant increase in the age-standardised incidence rate for invasive (AAPC 2.1%) and in situ melanoma (AAPC 6.5%). In conclusion, the incidence of melanoma has continued to increase in the elderly population over recent decades, with a rapidly increasing trend of in situ melanomas and the lentigo maligna subtype.