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Background: Ultraviolet radiation (UVR) is the major risk factor for development of malignant melanoma. Fibroblast activation protein (FAP)-alpha is a serine protease expressed on the surface of activated fibroblasts, promoting tumour invasion through extracellular matrix (ECM) degradation. The signalling mechanism behind the upregulation of FAP-alpha is not yet completely revealed. Methods: Expression of FAP-alpha was analysed after UVR exposure in in vitro co-culture systems, gene expression arrays and artificial skin constructs. Cell migration and invasion was studied in relation to cathepsin activity and secretion of transforming growth factor (TGF)-beta 1. Results: Fibroblast activation protein-a expression was induced by UVR in melanocytes of human skin. The FAP-alpha expression was regulated by UVR-induced release of TGF-beta 1 and cathepsin inhibitors prevented such secretion. In melanoma cell culture models and in a xenograft tumour model of zebrafish embryos, FAP-alpha mediated ECM degradation and facilitated tumour cell dissemination. Conclusions: Our results provide evidence for a sequential reaction axis from UVR via cathepsins, TGF-beta 1 and FAP-alpha expression, promoting cancer cell dissemination and melanoma metastatic spread., Funding Agencies|Swedish Research Council; Welander-Finsen Foundation; Ostgotaregionens Cancer Foundation; Swedish Cancer Society; County Council of Ostergotland; Olle Engkvist Foundation

Introduction: Skin diseases are among the five most common health problems in Nepal. We have now tested the validity of mobile teledermatology with mobile phones to find a safe and easy way of diagnosis and treatment of skin diseases for the most vulnerable people in remote areas without access to derma­ tologists. Methods: A medical officer at a primary health care centre examined the patient, obtained information of the patient and the skin disease, took photographs of the skin lesions. Then he transmitted all these data via Viber to a dermatologist in Kathmmandu, who in real time formulated diagnosis and treatment and sent it via Viber to the medical officer. Subsequently the patient was examined face to face by a blinded dermatologist at the same primary health care centre. The time taken for each modality of consultation was recorded .A third dermatologist analysed and compared the diagnoses formulated during telederma­ tology and the face to face consultations. Results: Altogether 107 skin diseases were diagnosed in 101 patients. There was an overall concordance of 88% between the diagnoses of skin diseases by mobile teledermatology and face to face consultations (Cohen k coefficient 0.85). The average face to face consultation time was 5 minutes, while it was 7 min­ utes more for teleconsultation. More than 75% of the photos were of good quality. Conclusions: Mobile teledermatology using smartphones is a reliable, useful, cost effective method to provide expertise for improving dermatologic care for the needy population in rural and remote parts of Nepal.

Ultraviolet (UV) irradiation induces skin pigmentation, which relies on the intercellular crosstalk of melanin between melanocytes to keratinocytes. However, studying the separate effects of UVA and UVB irradiation reveals differences in cellular response. Herein, we show an immediate shedding of extracellular vesicles (EVs) from the plasma membrane when exposing human melanocytes to UVA, but not UVB. The EV-shedding is preceded by UVA-induced plasma membrane damage, which is rapidly repaired by Ca2+-dependent lysosomal exocytosis. Using co-cultures of melanocytes and keratinocytes, we show that EVs are preferably endocytosed by keratinocytes. Importantly, EV-formation is prevented by the inhibition of exocytosis and increased lysosomal pH but is not affected by actin and microtubule inhibitors. Melanosome transfer from melanocytes to keratinocytes is equally stimulated by UVA and UVB and depends on a functional cytoskeleton. In conclusion, we show a novel cell response after UVA irradiation, resulting in transfer of lysosome-derived EVs from melanocytes to keratinocytes., Funding Agencies|Swedish Research Council; Swedish Cancer Society; Welander-Finsen Foundation; County Council of Ostergotland; Stiftelsen Olle Engkvist Byggmastare; Konung Gustav V och Drottning Victorias Frimurarestiftelse; Ostgotaregionens Cancerfond

Ultraviolet (UV) irradiation is a risk factor for development of malignant melanoma. UVA-induced lysosomal exocytosis and subsequent cell growth enhancement was studied in malignant melanoma cell lines and human skin melanocytes. UVA irradiation caused plasma membrane damage that was rapidly repaired by calcium-dependent lysosomal exocytosis. Lysosomal content was released into the culture medium directly after irradiation and such conditioned media stimulated the growth of non-irradiated cell cultures. By comparing melanocytes and melanoma cells, it was found that only the melanoma cells spontaneously secreted cathepsins into the surrounding medium. Melanoma cells from a primary tumour showed pronounced invasion ability, which was prevented by addition of inhibitors of cathepsins B, D and L. Proliferation was reduced by cathepsin L inhibition in all melanoma cell lines, but did not affect melanocyte growth. In conclusion, UVA-induced release of cathepsins outside cells may be an important factor that promotes melanoma growth and progression., Funding Agencies|Swedish Research Council; Ostgotaregionens Cancer Foundation; Stiftelsen Olle Engkvist Byggmastare; Swedish Cancer Society; Welander-Finsen Foundation

BACKGROUND: Ultraviolet (UV) radiation constitutes an important risk factor for malignant melanoma, but the wavelength responsible for the initiation of this disease is not fully elucidated. Solar UV induces multiple signalling pathways that are critical for initiation of apoptotic cell death as a cellular defence against malignant transformation. OBJECTIVES: To evaluate the involvement of the transcription factors nuclear factor (NF)-κB and activator protein (AP)-1 in the signalling pathways induced by UVA or UVB irradiation in human melanocytes. METHODS: Primary cultures of normal human melanocytes were irradiated with UVA or UVB, and the concomitant DNA damage and redox alterations were monitored. The resulting activation of the NF-κB and AP-1 signalling pathways and subsequent apoptosis were studied. RESULTS: UVB irradiation causes DNA damage detected as formation of cyclobutane pyrimidine dimers, while UVA induces increased levels of 8-hydroxydeoxyguanosine and lipid peroxidation. UVA and UVB initiate phosphorylation of c-Jun N-terminal protein kinase and extracellular signal-regulated kinase, and the apoptosis signalling pathways converge into a common mechanism. Downregulation of c-Jun suppresses AP-1-mediated signalling and prevents apoptosis upstream of lysosomal and mitochondrial membrane permeabilization, whereas inhibition of NF-κB by SN50 increases apoptosis. CONCLUSIONS: We conclude that AP-1 induces proapoptotic signalling, whereas NF-κB is a key antiapoptotic/prosurvival factor in both UVA- and UVB-induced cellular damage in human melanocytes, which might in turn impact melanoma development and progression., Funding text:This study was supported by the Swedish Research Council, the Swedish Cancer Society, the County Council of Ostergotland, Konung Gustav V och Drottning Victorias Frimurarestiftelse and the Welander-Finsen Foundation.

Introduction: Skin diseases are a common cause of morbidity in Nepal as per the health services report. There is limited information on the prevalence and pattern of skin diseases in the community. The objective of this study was to determine the pattern of skin diseases in a rural village development community of Nepal. Materials and methods: Two dermatologic health camps were conducted, during which, the villagers were examined by dermatologists. The skin diseases diagnosed were recorded in a proforma. Results: There were 433 individuals examined and 359 (male-47.9%; female-52.1%) had skin disease identified clinically (camp prevalence- 83%). The age of patients ranged from 1 to 80 years (mean-24.5; SD±15.9), with majority in the age group of 10-19 years. The most common skin disease category was eczemas (36.4%), followed by infections (28.4%), acne (22%), pigment disorders (34%) and urticaria (12.3%). Conclusion: Skin diseases were common in the community. The five most common Skin disease categories were eczemas, infections, acne and pigment disorders were the more common conditions.

The p53 pathway regulates stress response, and variations in p53, MDM2, and MDM4 may predispose an individual to tumor development. The aim of this study was to study the impact of genetic variation on sporadic and hereditary melanoma. We have analyzed a combination of three functionally relevant variants of the p53 pathway in 258 individuals with sporadic malignant melanomas, 50 with hereditary malignant melanomas, and 799 healthy controls. Genotyping was performed by PCR-restriction fragment length polymorphism, pyrosequencing, and allelic discrimination. We found an increased risk for hereditary melanoma in MDM2 GG homozygotes, which was more pronounced among women (P=0.035). In the event of pairwise combinations of the single nucleotide polymorphisms, a risk elevation was shown for MDM2 GG homozygotes/p53 wild-type Arg in hereditary melanoma (P=0.01). Individuals with sporadic melanomas of the superficial spreading type, including melanoma in situ, showed a slightly higher frequency of the MDM2 GG genotype compared with those with nodular melanomas (P=0.04). The dysplastic nevus phenotype, present in the majority of our hereditary melanoma cases and also in some sporadic cases, further enhanced the effect of the MDM2 GG genotype on melanoma risk (P=0.005). In conclusion, the results show an association between MDM2 SNP309 and an increased risk for hereditary melanoma, especially among women. Analysis of sporadic melanoma also shows an association between MDM2 and the superficial spreading melanoma subtype, as well as an association with the presence of dysplastic nevi in sporadic melanoma.

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Ultraviolet (UV) irradiation is a major environmental carcinogen involved in the development of skin cancer. To elucidate the initial signaling during UV-induced damage in human keratinocytes, we investigated lysosomal exocytosis and apoptosis induction. UVA, but not UVB, induced plasma membrane damage, which was repaired by Ca2+-dependent lysosomal exocytosis. The lysosomal exocytosis resulted in extracellular release of cathepsin D and acid sphingomyelinase (aSMase). Two hours after UVA irradiation, we detected activation of caspase-8, which was reduced by addition of anti-aSMAse. Furthermore, caspase-8 activation and apoptosis was reduced by prevention of endocytosis and by the use of cathepsin inhibitors. We conclude that lysosomal exocytosis is part of the keratinocyte response to UVA and is followed by cathepsin-dependent activation of caspase-8. The findings have implications for the understanding of UV-induced skin damage and emphasize that UVA and UVB initiate apoptosis through different signaling pathways in keratinocytes., The previous status of this article was manuscript with the title Lysosomal exocytosis repairs the plasma membrane after UVA and is followed by caspase-8 induced apoptosis.

Introduction: Skin diseases (SDs) are one of the most common health problems in Nepal. The objectives of this study are to determine the prevalence of SDs and impact on quality of life (QoL) in a rural community in Nepal. Methods: A house-to-house survey was conducted in a community with 3,207 inhabitants, to obtain socio-demographic data and identify individuals with SDs. Free examination and treatment was offered at 4 health camps. Individuals with long-standing SDs were interviewed using the Dermatology Life Quality Index (DLQI). Results: Of 735 individuals attending the health camps, 645 (mean age 24.9 years, range 0.5-90) had one or more SDs. The overall prevalence of SDs was 20.1% (males 18.1%, females 22.5% and children 28.2%). The most common SD categories were eczemas (12.2%), pigment disorders (4.1%), acne (2.7%), urticaria (2.4%) and moles and lumps (1.6%). In the Nepalese culture, the DLQI question on sexuality was too direct so only 9/10 questions were used. In the 75 patients who were interviewed, the mean DLQI score was 10.7 (range 7-19), indicating a large impact on QoL. Conclusions: This population-based study shows that SDs were very common in a rural community in Nepal. The five most common SD categories comprise 77% of all SDs. Targeted training should enable health-care workers to prevent, accurately diagnose and manage these problems on site. An appropriate instrument to measure QoL adjusted to the socio-cultural norms of Nepal has to be developed.

Fibroblast activation protein-alpha (FAP-alpha) promotes tumor growth and cell invasiveness through extracellular matrix degradation. How ultraviolet radiation (UVR), the major risk factor for malignant melanoma, influences the expression of FAP-alpha is unknown. We examined the effect of UVR on FAP-alpha expression in melanocytes, keratinocytes and fibroblasts from the skin and in melanoma cells. UVR induces upregulation of FAP-alpha in fibroblasts, melanocytes and primary melanoma cells (PM) whereas keratinocytes and metastatic melanoma cells remained FAP-alpha negative. UVA and UVB stimulated FAP-alpha-driven migration and invasion in fibroblasts, melanocytes and PM. In co-culture systems UVR of melanocytes, PM and cells from regional metastases upregulated FAP-alpha in fibroblasts but only supernatants from non-irradiated PM were able to induce FAP-alpha in fibroblasts. Further, UV-radiated melanocytes and PM significantly increased FAP-alpha expression in fibroblasts through secretory crosstalk via Wnt5a, PDGF-BB and TGF-beta 1. Moreover, UV radiated melanocytes and PM increased collagen I invasion and migration of fibroblasts. The FAP-alpha/DPPIV inhibitor Gly-ProP(OPh)(2) significantly decreased this response implicating FAP-alpha/DPPIV as an important protein complex in cell migration and invasion. These experiments suggest a functional association between UVR and FAP-alpha expression in fibroblasts, melanocytes and melanoma cells implicating that UVR of malignant melanoma converts fibroblasts into FAP-alpha expressing and ECM degrading fibroblasts thus facilitating invasion and migration. The secretory crosstalk between melanoma and tumor surrounding fibroblasts is mediated via PDGF-BB, TGF-beta 1 and Wnt5a and these factors should be evaluated as targets to reduce FAP-alpha activity and prevent early melanoma dissemination.

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Cutaneous melanoma is characterized by poor patient outcome in its later stages. The search for genetic markers is therefore crucial for the identification of populations at risk for melanoma. Highly polymorphic CA repeats in 3 proximity in the MANBA gene were examined by PCR-capillary electrophoresis in 185 Swedish melanoma patients and 441 tumor-free age- and gender-matched individuals. The associations of the polymorphisms with melanoma risk, the pigment phenotypes of the patients and tumor characteristics were analyzed. A significant difference in allelic distribution between melanoma patients and tumor-free individuals was observed. The frequency of the MANBA genotype <21CAs/>= 21CAs was significantly higher in melanoma patients than in the controls. When comparing allele distribution in patients and their matched controls, the allele <21 CAs was found to be associated with the female gender (39.8 vs. 31.2%, P=0.041, OR=1.46, 95% Cl 1.02-2.10), but not with male gender (34.4 vs. 30.9%, P=0.39). Within the melanoma group, there were no differences in the distribution of the MANBA alleles associated with patient gender or age before or after 55 years at diagnosis, nor was there any association between the MANBA genotype and pigment phenotype or tumor sites. The MANBA allele <21CAs was, however, associated with thin melanomas at diagnosis (Breslow thickness <= 1.5 mm and Clark levels I and II). In conclusion, these data suggest that MANBA polymorphisms might be an indicator of tumor growth and progression and, together with other markers, could be used to identify individuals at increased risk of melanoma.

The annual cost of skin cancer in Sweden in 2005 was estimated to be -142.4 million (-15/inhabitant). When comparing direct costs only cost associated with medical consumption, skin cancer is more costly than the equivalent costs of both multiple sclerosis and brain tumours, and is close to the cost of breast cancer.

Skin cancer is one of the most rapidly increasing cancers among the Swedish population and a significant cause of illness and death. This study aims to estimate the total societal cost of skin cancer in Sweden 2005, using a prevalence based cost-of-illness approach. The total cost of skin cancer was estimated to € 142.4 million (€ 15 per inhabitant), of which € 79.6 million (€ 8 per inhabitant) were spent on health services and € 62.8 million (€ 7 per inhabitant) were due to production loss. The main cost driver was resource utilisation in outpatient care, amounting to 42.2% of the total cost. Melanoma was the most costly skin cancer diagnosis. Non-melanoma skin cancer was however the main cost driver for health services alone. In the future it is important to establish effective preventive measures to avoid increasing costs and suffering caused by skin cancer., Original publication: Gustav Tinghög, Per Carlsson, Ingrid Synnerstad and Inger Rosdahl, Societal Cost of Skin Cancer in Sweden 2005, 2008, Acta Dermato-Venereologica, (88), 5, 467-473.http://dx.doi.org/10.2340/00015555-0523. Copyright © Taylor & Francis Group, an informa business

Background: There is a possible association between atopy and cancer based on the concept of atopic diseases as a hyper-reactive state of the immune system. Melanoma is an immunogenic tumour, and since patients with atopic dermatitis (AD) are subjected to local and systemic immunosuppressives, it would be expected to find an influence of AD on the melanoma risk. There is a positive correlation between the number of naevi and melanoma risk, and children and adults with AD have fewer naevi than controls although many patients receive ultraviolet treatment. Objective: This study aims to investigate the melanoma risk in a retrospective cohort of AD patients compared with the population. Study design: 6280 AD patients born 1935–1979 visited five Dermatology clinics during 1986–2004. Mean follow-up time was 36.7 years (SD 6.9) corresponding to 230 742 person-years at risk. The cohort file was linked to the National Cancer register. Results: Six AD patients with melanoma were identified, and the Poisson regression analysis adjusted for age group, sex and year resulted in an incidence rate ratio of 0.49 (95% confidence interval: 0.27–1.35, P = 0.08) for the AD group compared with the total population in the region. Conclusion: A low risk to develop melanoma was found in AD patients. However, the results must be interpreted with caution since the small number of expected cases of melanoma makes the risk estimate sensitive to chance effects. We hypothesize that formation of naevi and progression to melanoma is counteracted by the inflammatory process in the skin of AD patients.

The Xeroderma pigmentosum complementation group D (XPD) is a critical protein in the nucleotide excision repair system for DNA damage. Genetic variations in XPD exert an important effect on the capacity of DNA repair. In this study, we examined Lys751Gln polymorphism at the XPD gene in 244 melanoma patients and 251 healthy individuals (as controls) from the south-eastern region of Sweden. The associations of polymorphism with melanoma risk, as well as with melanoma features and pigment phenotypes of the melanoma patients were analysed. DNA was extracted from the mononuclear cells of venous blood of the melanoma patients and controls. XPD codon 751 was genotyped by the PCR restriction fragment length polymorphism technique. Results showed that there was no difference in the distribution of the XPD codon 751 genotypes between the melanoma patients and healthy controls. However, the Gln/Gln genotype was found to be associated with melanoma risk in the male population. Furthermore, the frequency of the Gln/Gln genotype was significantly higher in the early stages of melanomas, whereas Lys/ Gln was more frequent in the later stages and in the patients with melanoma located on intermittently UV-exposed areas. No correlations between the polymorphisms and phenotypes of the patients were found. In conclusion, Gln/Gln was a useful genetic marker for melanoma risk in the males, while Lys/Gln was an important predictor for melanoma progression.

The Xeroderma pigmentosum complementation group D (XPD) is a critical protein in the nucleotide excision repair system for DNA damage. Genetic variations in XPD exert an important effect on the capacity of DNA repair. In this study, we examined Lys751Gln polymorphism at the XPD gene in 244 melanoma patients and 251 healthy individuals (as controls) from the south-eastern region of Sweden. The associations of polymorphism with melanoma risk, as well as with melanoma features and pigment phenotypes of the melanoma patients were analysed. DNA was extracted from the mononuclear cells of venous blood of the melanoma patients and controls. XPD codon 751 was genotyped by the PCR restriction fragment length polymorphism technique. Results showed that there was no difference in the distribution of the XPD codon 751 genotypes between the melanoma patients and healthy controls. However, the Gln/Gln genotype was found to be associated with melanoma risk in the male population. Furthermore, the frequency of the Gln/Gln genotype was significantly higher in the early stages of melanomas, whereas Lys/Gln was more frequent in the later stages and in the patients with melanoma located on intermittently UV-exposed areas. No correlations between the polymorphisms and phenotypes of the patients were found. In conclusion, Gln/Gln was a useful genetic marker for melanoma risk in the males, while Lys/Gln was an important predictor for melanoma progression.

In this study, functional polymorphisms of NF-κB1 and NF-κBIα genes were examined in 185 melanoma patients and 438 tumor-free individuals. Associations of the polymorphisms with melanoma risk, age and pigment phenotypes of the patients and clinico-pathological tumor characteristics were analyzed. DNAs were isolated from mononuclear cells of venous blood. Polymorphisms of the genes were genotyped by a PCR-RFLP technique, and transcription level of NF-κBIα was examined by a quantitative real-time reverse transcription PCR. Results showed that both ATTG insertion polymorphism of NF-κB1 and A to G polymorphism of NF-κBIα genes were correlated with melanoma risk, especially, in a combination of ATTG2/ATTGT2 and GG. NF-κB1 ATTG2/ATTG2 and NF-κBIα GG genotypes were associated with male gender and age > 65 years (at diagnosis). Patients with ATTG1/ATTG1 genotype had thinner tumors and lower Clark levels at diagnosis. Frequency of ATTG1/ATTG1 genotype was higher in patients with melanomas on intermittently sun-exposed pattern of the body and NF-κBIα GG was more frequent in the patients with melanomas at rarely exposed sites. There were no differences in the gene transcription level between patients with different NF-κBIα genotypes. These data suggest that NF-κB1 and NF-κBIα genes might be susceptible genes for melanoma risk and functional polymorphisms of these genes might be biological predictors for melanoma progression., The original publication is available at www.springerlink.com: Huajie Bu, Inger Rosdahl, XiaoFeng Sun, Katarina Holmdahl-Källenand and Hong Zhang, Importance of polymorphisms at NF-κB1 and NF-κBIα genes in melanoma risk, clinicopathological features and tumor progression in Swedish melanoma patients, 2007, Journal of Cancer Research and Clinical Oncology, (133), 11, 859-866. http://dx.doi.org/10.1007/s00432-007-0228-7 . Copyright: Springer-Verlag, www.springerlink.com

Polymorphisms of GSTM1, GSTT1 and GSTP1 were examined in melanoma patients and tumor-free individuals. Relationships between the polymorphisms and tumor characteristics and pigment phenotypes of the patients were analyzed. There was no significant difference in GSTM1 null and GSTT1 null genotypes nor GSTP1 GG genotype between melanoma patients and controls. In melanoma patients, these polymorphisms were not correlated with early or later onset of melanomas or gender of the patients. Frequency of GSTM1 null genotype was higher in patients with melanoma >2.5 mm than in those with tumors <1.0 mm, and higher frequency was found in nodular melanoma than in the other tumor types. GSTP1 GG genotype was more often found in the patients with brown and mixed eye color or brown and black hair than those with blue and green eyes or blond hair. It is unlikely that polymorphisms of GSTM1, GSTT1 and GSTP1 are general risk factors for melanoma in the Swedish population. GSTM1 null genotype was correlated with Breslow thickness and tumor type, which might serve as an additional biomarker for a rapid tumor progression. GSTP1 GG increases risk for melanoma in the subgroup of individuals with dark eyes or hair.

PURPOSE: Human skin melanoma at later stages usually has an extremely poor prognosis. It is of importance to search for biologic markers to identify and monitor individuals at risk for melanoma for early diagnosis and to avoid tumor progression. The FAS gene and its natural ligand (FASL) gene initiate the death signal cascade, playing a central role in the apoptotic signaling pathway and tumor growth and metastasis. PATIENTS AND METHODS: In this study, we analyzed polymorphisms in 229 patients with melanoma and 351 age- and gender-matched tumor-free individuals. Genomic DNAs were isolated from mononuclear cells in peripheral vein blood, and the polymorphisms were examined with polymerase chain reaction-restriction fragment length polymorphism techniques. Frequency in distribution of the polymorphisms was compared between the patients with melanoma and the healthy control subjects, and associations with patients' pigment phenotypes, age at diagnosis, and melanoma characteristics were analyzed. RESULTS AND CONCLUSIONS: The FAS-1377, FAS-670, and FASL-844 polymorphisms were not found to be markers of melanoma risk (P > 0.05). In patients with melanoma, frequencies of the FAS-1377, FAS-670, and FASL-844 polymorphisms were different between the patients aged <50 and > or =50 years (P < or = 0.025, P < or = 0.025, and P < or = 0.01). Moreover, the FAS-670 polymorphism correlated with tumor Breslow thickness (P < or = 0.01) and Clark level (P < or = 0.001) and was associated with tumors developing in sun-exposed locations (P < or = 0.001). FAS and FASL were not markers for melanoma risk but might be important in the development and progression of sun-induced melanoma independently of skin type.

Purpose To evaluate a program initiated in 1987 by the Swedish Melanoma Study Group aiming to provide preventive surveillance to kindreds with hereditary cutaneous melanoma and dysplastic nevus syndrome. Patients and Methods Overall, 2,080 individuals belonging to 280 melanoma families were followed for 14 years between 1987 and 2001 at 12 participating centers. Data were registered in a central database. Results Among 1,912 skin lesions excised during follow-up, 41 melanomas were removed in 32 individuals. Of these, 15 (37%) were in situ melanomas and 26 (63%) invasive melanomas. The median tumor thickness of invasive melanomas was 0.5 mm. Ulceration was absent in 24 of 26 invasive melanomas (92%) and 12 (46%) lacked vertical growth phase. Compared with melanomas in the general Swedish population, the melanomas identified in these kindreds during follow-up had better prognostic characteristics. All melanomas except one were diagnosed in families with two or more first-degree relatives with melanoma. Diagnosis of melanoma occurred in three of eight kindreds with germline CDKN2A mutations, supporting that families with such mutations are at increased risk for melanoma development. Of the 32 individuals who developed melanoma during follow-up, 21 (66%) had had at least one previously diagnosed melanoma. Conclusion This study shows that a coordinated program aimed at detecting and offering skin surveillance in kindreds with hereditary cutaneous melanoma results in a low incidence of melanomas during the follow-up period and that the tumors that do arise have favorable prognostic characteristics.

Malignant melanoma is the most common cancer during pregnancy, but it is unknown whether melanocytic naevi in general are activated. A total of 381 melanocytic naevi in 34 Caucasian primigravidae were examined using spectrophotometric intracutaneous analysis (SIAscopy) technology in early pregnancy and prior to delivery. The Siagraphs of each naevus were then compared in order to evaluate changes over time. A total of 163 melanocytic naevi in 21 nulliparous women served as an additional control group. At the first visit none of the Siagraphs examined for the case or control groups aroused suspicion of dysplastic naevus or melanoma and no significant structural changes were noted during the observation period. However, 2.1% of the melanocytic naevi in the pregnant group increased and 1.3% decreased in size. Corresponding figures in the non-pregnant group were 1.8% and 0%, respectively. Only one naevus in a pregnant woman increased slightly in epidermal pigmentation, and a decrease in pigmentation was noted in 3.7% of the melanocytic naevi in the cases and 1.8% in the controls. None of the differences within or between the groups was statistically significant. We conclude that pregnancy does not influence the appearance of pigmented naevi. A changing naevus during pregnancy should be examined carefully and considered for excision and histopathology. © 2007 Acta Dermato-Venereologica., DOI does not work: 10.2340/00015555-0227