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Using an experimental task in which lay persons were asked to distinguish between 30 images of melanomas and common mimics of melanoma, we compared various training strategies including the ABC(D) method, use of images of both melanomas and mimics of melanoma, and alternative methods of choosing training image exemplars. Based on a sample size of 976 persons, and an online experimental task, we show that all the positive training approaches increased diagnostic sensitivity when compared with no training, but only the simultaneous use of melanoma and benign exemplars, as chosen by experts, increased specificity and diagnostic accuracy. The ABCD method and use of melanoma exemplar images chosen by laypersons decreased specificity in comparison with the control. The method of choosing exemplar images is important. The levels of change in performance are however very modest, with an increase in accuracy between control and best-performing strategy of only 9%.

Robust experimental evidence supporting many attempts to facilitate early melanoma diagnosis is lacking. In an experimental study using a browser interface we have examined diagnostic accuracy, sensitivity and specificity of novices in distinguishing between melanomas and mimics of melanoma. We show that rule-based ABC methods and image training, based on random images of melanoma, improve specificity to similar degrees, with-out effects on sensitivity, leading to small improvements in overall accuracy. There was a significant effect of age with older subjects performing better. Although both the ABC method and image training groups showed improved performance over the control group, overall performance was poor. For instance, for a task in which 1 in 4 test images was a melanoma, and 3 out of 4 benign, both interventions (ABC or image training) increased accuracy from the control value of 53% to around 61%. For reference, dermatology trainees performed at a much higher level of accuracy. Our study provides little support for the use of such methods in public education, but suggests ways in which performance might be improved.

Traditional clinical teaching emphasises the importance of a full clinical examination. In the clinical assessment of lesions that may be skin cancer, full examination allows detection of incidental lesions, as well as helping in the characterisation of the index lesion. Despite this, a total body skin examination is not always performed. Based on two prospective studies of over 1,800 sequential patients in two UK centres we show that over one third of melanomas detected in secondary care are found as incidental lesions, in patients referred for assessment of other potential skin cancers. The majority of these melanomas occurred in patients whose index lesion turned out to be benign. Alternative models of care--for instance some models of teledermatology in which a total body skin examination is not performed by a competent practitioner--cannot be considered equivalent to a traditional consultation and, if adopted uncritically, without system change, will likely lead to melanomas being missed.

The "ABCD" mnemonic to assist non-experts' diagnosis of melanoma is widely promoted; however, there are good reasons to be sceptical about public education strategies based on analytical, rule-based approaches--such as ABCD (i.e. Asymmetry, Border Irregularity, Colour Uniformity and Diameter). Evidence suggests that accurate diagnosis of skin lesions is achieved predominately through non-analytical pattern recognition (via training examples) and not by rule-based algorithms. If the ABCD are to function as a useful public education tool they must be used reliably by untrained novices, with low inter-observer and intra-diagnosis variation, but with maximal inter-diagnosis differences. The three subjective properties (the ABCs of the ABCD) were investigated experimentally: 33 laypersons scored 40 randomly selected lesions (10 lesions × 4 diagnoses: benign naevi, dysplastic naevi, melanomas, seborrhoeic keratoses) for the three properties on visual analogue scales. The results (n = 3,960) suggest that novices cannot use the ABCs reliably to discern benign from malignant lesions.

Skin cancer is the commonest malignancy in most European populations, and is highly treatable. The highest density of tumours is on the face, ears and - if the patient is bald - the scalp. There are two main varieties of skin cancer with very different consequences: melanoma is uncommon but has a significant case-fatality of -20%, whereas keratinocyte tumours, such as basal cell carcinoma and squamous cell carcinoma, are more common, but have a much better prognosis than melanoma. Diagnosis of skin cancer relies on clinical suspicion and the ability to distinguish the morphologies typical of cancer from the far larger number of benign mimics of skin cancer. Clinical suspicion is paramount in achieving early diagnosis. [ABSTRACT FROM AUTHOR]

Non-analytical reasoning is thought to play a key role in dermatology diagnosis. Considering its potential importance, surprisingly little work has been done to research whether similar identification processes can be supported in non-experts. We describe here a prototype diagnostic support software, which we have used to examine the ability of medical students (at the beginning and end of a dermatology attachment) and lay volunteers, to diagnose 12 images of common skin lesions. Overall, the non-experts using the software had a diagnostic accuracy of 98% (923/936) compared with 33% for the control group (215/648) (Wilcoxon p < 0.0001). We have demonstrated, within the constraints of a simplified clinical model, that novices' diagnostic scores are significantly increased by the use of a structured image database coupled with matching of index and referent images. The novices achieve this high degree of accuracy without any use of explicit definitions of likeness or rule-based strategies. [ABSTRACT FROM AUTHOR]

Loss of genetic material, including loss of loci on chromosome arms 6q, 9p, and 10q, occurs frequently in cutaneous melanoma but infrequently in benign melanocytic nevi or other melanocytic lesions, suggesting that these genetic alterations are important in the development and progression of melanoma. To examine whether allelic loss is of prognostic importance in melanoma, disease-free survival was related to loss of heterozygosity on 6q, 9p and 10q in 83 individuals with sporadic primary cutaneous melanoma. Loss of chromosome arms 6q and 10q were each significantly associated with a poorer clinical outcome (P=0.013 and P=0.001 respectively). In a subgroup of 41 subjects whose primary tumours were allelotyped, the fractional allelic loss (FAL) at 39 autosomal arms also significantly correlated with disease-free survival (P=0.013), with an increase in FAL associated with a poorer outcome; this association remained significant when controlled for tumour thickness (P=0.035). In addition, a greater proportion of cells were immunopositive for Ki67 antigen, p53 and p21WAF1 protein in the primary melanomas than in the benign melanocytic nevi, however, only p53 over-expression was significantly associated with improved survival (P=0.041). [ABSTRACT FROM AUTHOR]

We have studied the cutaneous response to ultraviolet radiation, measured objectively as erythema in a sample of 12 body sites on 15 Northern European subjects with multiple doses of ultraviolet B (UVB). Skin pigmentation and the development of photoadaptation in response to five repeated doses of irradiation at three body sites was also measured. We report striking differences of up to 5-fold at different body sites to the same challenge dose (p<0.001) and demonstrate that for this population, site variation is just as important as between-person variation. Skin color at each body site is a strong predictor of response (p<0.001) and that this cannot be attributed to vascular differences, but instead we believe it reflects site-specific variations in melanin pigmentation. We also observed similar but smaller within-person effects for responses to another inflammatory agent, dithranol (p<0.01). Despite this, we did not find evidence for differences in the development of photoadaptation by body site. These results have clear clinical implications for the practice of phototesting prior to commencing phototherapy, for therapeutic failure in sites such as the legs in patients with psoriasis, and perhaps for melanoma body-site distribution. [ABSTRACT FROM AUTHOR]

Loss of heterozygosity of chromosome region 9p21 occurs commonly and early in sporadic melanoma, suggesting the involvement of a tumor suppressor gene at this locus in the pathogenesis of this neoplasm. Although germline mutations and deletions of the p16INK4 gene located at 9p2l have been reported in familial melanoma, the relative contributions of mutation and deletion in sporadic melanoma are at present unclear. In this study, we investigated 26 cases of sporadic cutaneous melanoma (14 of which demonstrated loss of heterozygosity at 9p2l) for mutations of p16INK4. One tumor with allelic loss of 9p contained a CC → TT mutation at codons &frac5758;, altering an arginine to a stop codon, consistent with bi-allelic inactivation of p16INK4 in this case. No mutations were identified in any of the other melanomas, or in one benign intradermal nevus with atypical features and two Spitz nevi that also showed loss of heterozygosity of 9p. The inactivation of both copies of p16INK4 in the one case of melanoma adds support to the theory that p16INK4 is important in the development of sporadic cutaneous melanoma, although allelic loss or other methods of inactivation of p16INK4 rather than point mutation appears to be numerically more important. The low frequency of mutation of p16INK4 in cases of sporadic melanoma with loss of heterozygosity of 9p is, however, also consistent with there being another tumor suppressor gene near this locus that is involved in some cases of sporadic melanoma. [ABSTRACT FROM AUTHOR]

Variation in skin color is the major host risk factor for melanoma and other forms of skin cancer. Individuals with red hair show an increased ratio of phaeomelanin to eumelanin in both hair and skin. This ratio is regulated by the melanocortin (MC) 1 receptor. There are several common point mutations in the human MC1 receptor that are overrepresented in North European red-heads, and in individuals with pale skin. In order to determine the functional significance of these mutations, we expressed the Asp84Glu, Val92Met, Arg163Gln, and Asp294His variants of the human MC1 receptors in eukaryotic cells and determined their ability to bind α-melanocyte stimulating hormone (MSH) peptides and increase intracellular cAMP. The mutants Asp84Glu and Asp294His showed a much lower response to α-MSH in cAMP and a slightly impaired ability to bind α-MSH, and the Val92Met mutant bound α-MSH with 100-fold lower affinity as compared with the wild-type. The Arg163Gln variant, widely found in some Asian populations, reached normal level of cAMP response but had just slightly lower potency for α-MSH in binding and second messenger studies. The results provide important pharmacological characterization of common MC1 receptor variants in various world populations. [ABSTRACT FROM AUTHOR]

Microsatellite instability secondary to replication errors (RER), characterized by length changes at repetitive loci scattered throughout the genome, is a recently recognized genetic mechanism important in the development of some human cancers. Although RER has been reported in sebaceous gland tumors from patients with the Muir-Torre syndrome, the frequency of RER in human non-melanoma and melanoma skin cancers is not known. In this study, we investigated the importance of RER in human skin carcinogenesis. RER was identified in three of four actinic keratoses from a patient belonging to a kindred with documented Muir-Tone syndrome, which indicates that defective DNA replication may contribute to skin cancer development in such patients. Examination of a series of tumors from patients without Muir-Torre, Including 137 skin cancers (47 basal cell carcinomas, 49 squamous cell carcinomas, and 41 primary malignant melanomas), 19 actinic keratoses, and 20 cases of Bowen's disease, using 10 or more microsatellite markers, identified repeat- sequence instability in less than 5% of the tumors studied, In six of the eight tumors, the sole change was an alteration 2 base pairs in length at a single locus, One patient with a squamous cell carcinoma showed changes at multiple loci suggesting defective mismatch repair. Although the low frequency of RER found in this study of a large series of human skin tumors suggests that this phenomenon is uncommon in patients with skin cancer, the identification of RER at multiple loci in two patients suggests that error-prone replication may be important in skin cancer development in some individuals. [ABSTRACT FROM AUTHOR]

Focuses on skin types, melanoma, and melanocortin 1 receptor (MC1R) variants. Associations between particular variants of the MC1R and skin type and melanoma; Variants associated with red hair; Overall frequency of MC1R variants in melanoma patients.