Metastatic disease is the primary cause of death in cutaneous malignant melanoma (CMM) patients. To understand the mechanisms of CMM metastasis and identify potential predictive markers, we analyzed gene-expression profiles of 34 vertical growth phase melanoma cases using cDNA microarrays. All patients had a minimum follow-up of 36 months. Twenty-one cases developed nodal metastatic disease and 13 did not. Comparison of gene expression profiling of metastatic and nonmetastatic melanoma cases identified 243 genes with a >2-fold differential expression ratio and a false discovery rate of <0.2 (206 up-regulated and 37 down-regulated). This set of genes included molecules involved in cell cycle and apoptosis regulation, epithelial-mesenchymal transition (EMT), signal transduction, nucleic acid binding and transcription, protein synthesis and degradation, metabolism, and a specific group of melanoma-and neural-related proteins. Validation of these expression data in an independent series of melanomas using tissue microarrays confirmed that the expression of a set of proteins included in the EMT group (N-cadherin, osteopontin, and SPARC/osteonectin) were significantly associated with metastasis development. Our results suggest that EMT-related genes contribute to the promotion of the metastatic phenotype in primary CMM by supporting specific adhesive, invasive, and migratory properties. These data give a better understanding of the biology of this aggressive tumor and may provide new prognostic and patient stratification markers in addition to potential therapeutic targets. [Cancer Res 2007;67(7):3450-60]
The onset of FD before 25 years of age and the presence of pustules within the alopecic patch were associated with severe FD. Tetracyclines and the combination of clindamycin and rifampicin were the most useful treatments.
The aim of this study was to identify factors related to lip cancer (LC) considering individual characteristics and sociodemographic factors. A case -control study was carried out in the province of Granada (Andalusia, southern Spain). The cases were 105 males with squamous-cell carcinoma of the lip, diagnosed between 1987 and 1989 (aged 20 -70 years) and identified by means of a populationbased Cancer Registry. As controls, a randomised populational sample of 239 males, stratified by age, was used. Multiple logistic regression analysis showed that risk factors are lifetime cumulative tobacco consumption and alcohol consumption. An interaction was found between alcohol consumption and the smoking habit (leaving the cigarette on the lip): OR ¼ 23.6; 95% CI: 3.9 -142.0. Other risk factors identified are clear eyes (OR ¼ 3.5; CI: 95% 1.5 -8.0), sun exposure early in life and cumulative sun exposure during outdoor work (OR ¼ 11.9; 95%: CI: 1.3 -108.9), and skin reaction to sun exposure (Fitzpatrick levels). Another interaction was found between skin reaction and a previous history of common sporadic warts (OR ¼ 4.4; 95% CI: 1.01 -19.1). We conclude that LC is related to phenotype, skin reaction to sun exposure, cumulative and early sunlight exposure, and tobacco and alcohol consumption, as well as a low educational level. Leaving the cigarette on the lip is predictive of LC risk irrespective of cumulative tobacco consumption.
The main objective of this study was to assess the influence of sun exposure and pigmentary traits on the risk of cutaneous malignant melanoma (CMM) in a Mediterranean population (Andalusia, southern Spain). Cases and controls were selected from 1988 to 1993. The study population included 105 incident cases with non-familial CMM (ICD-9 code 172) and 138 controls aged 20 to 79 years. Data were collected by personal interview, and melanocytic nevi were counted over the entire body surface. Crude, and multiple-risk factor adjusted, odds ratios (OR) and their 95 percent confidence intervals (CI) were computed. After adjustment, the major constitutional risk factor was skin type I-II (OR = 29.8, CI = 8.9-100) compared with skin type V. Statistically significant and positive trends were observed between the risk of CMM and occupational sun exposure of the skin (P = 0.003), recreational exposure (P < 0.001), and cumulative lifetime sun exposure (P < 0.001). Several characteristics related to sun exposure during summer increased the CMM risk, e.g., episodes of blistering sunburns and the number of sunbaths in childhood. Use of sunscreens and spending summer holidays in places other than beach were associated with a lower risk of CMM. Regarding pigmentary traits, CMM significantly occurred with more frequency in individuals with a high degree of freckling and quoted numbers of melanocytic nevi. In conclusion, the results support sun exposure and pigmentary traits (skin type, melanocytic nevi, and freckles) as main risk factors for CMM in this population.
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