Fabrizio Ayala

Discrepant alterations in main candidate genes among multiple primary melanomas

BackgroundAlterations in key-regulator genes of disease pathogenesis (BRAF, cKIT, CyclinD1) have been evaluated in patients with multiple primary melanoma (MPM).MethodsOne hundred twelve MPM patients (96 cases with two primary melanomas, 15 with three, and 1 with four) were included into the study. Paired synchronous/asynchronous MPM tissues (N = 229) were analyzed for BRAF mutations and cKIT/CyclynD1 gene amplifications.ResultsBRAF mutations were identified in 109/229 (48%) primary melanomas, whereas cKIT and CyclinD1 amplifications were observed in 10/216 (5%) and 29/214 (14%) tumor tissues, respectively. While frequency rates of BRAF mutations were quite identical across the different MPM lesions, a significant increase of cKIT (p < 0.001) and CyclinD1 (p = 0.002) amplification rates was observed between first and subsequent primary melanomas. Among the 107 patients with paired melanoma samples, 53 (49.5%) presented consistent alteration patterns between first and subsequent primary tumors. About one third (40/122; 32.8%) of subsequent melanomas presented a discrepant pattern of BRAF mutations as compared to incident primary tumors.ConclusionsThe low consistency in somatic mutation patterns among MPM lesions from same patients provides further evidence that melanomagenesis is heterogeneous and different cell types may be involved. This may have implications in clinical practice due to the difficulties in molecularly classifying patients with discrepant primary melanomas.

MDM2 SNP309 and p53 Arg72Pro in cutaneous melanoma: association between SNP309 GG genotype and tumor Breslow thickness

A functional single nucleotide polymorphism (SNP) 309 T/G within mouse double minute 2 (MDM2) gene has been linked to onset and outcome of disease in tumors. Two published studies have shown discordant results regarding the effect of this SNP on age at diagnosis of cutaneous melanoma (CM) in Caucasian female populations. Here, we examined the age at diagnosis and clinical associations of CM with SNP309 and the related polymorphism, p53 Arg72Pro, in an Italian population (249 CM patients and 291 cancer-free controls) composed of women and men. MDM2 intronic region of 294 bp was directly sequenced, whereas Arg72Pro SNP was analyzed by polymerase chain reaction-restriction fragment length polymorphism. No associations were found among the SNP309, Arg72Pro, risk of CM, age at diagnosis and presence of metastasis in total subjects and when stratified according to the gender. The SNP309 was significantly associated with tumor Breslow thickness. The P-value in the minor allele recessive mode was 0.02, and the odds ratio (OR) adjusted for gender and age was 3.11 (95% confidential interval (CI)=1.21–8.00). The SNP309 is not associated with the risk and age of onset of CM, and the presence of metastasis in an Italian population but the SNP309 GG may be a risk genotype for increasing in tumor Breslow thickness.

The role of optical radiations in skin cancer.

Purpose. Electromagnetic radiation with wavelength in the range 100 nm to 1 mm is known as optical radiation and includes ultraviolet radiation, the visible spectrum, and infrared radiation. The deleterious short- and long-term biological effects of ultraviolet radiation, including melanoma and other skin cancers, are well recognized. Infrared radiation may also have damaging biological effects. Methods. The objective of this review was to assess the literature over the last 15 years and to summarize correlations between exposure to optical radiation and the risk of melanoma and other cancers. Results. There is a clear correlation between exposure to UV radiation and the development of skin cancer. Most importantly, a strong association between artificial UV radiation exposure, for example, tanning devices, and the risk of melanoma and squamous cell carcinoma has been clearly demonstrated. There is no clear evidence that exposure to IR and laser radiation may increase the risk of skin cancer, although negative health effects have been observed. Conclusions. Preventative strategies that involve provision of public information highlighting the risks associated with exposure to sunlight remain important. In addition, precautionary measures that discourage exposure to tanning appliances are required, as is legislation to prevent their use during childhood.

Sun exposure and melanoma prognostic factors

Previous studies have reported an association between sun exposure and the increased survival of patients with cutaneous melanoma (CM). The present study analyzed the association between ultraviolet (UV) light exposure and various prognostic factors in the Italian Clinical National Melanoma Registry. Clinical and sociodemographic features were collected, as well as information concerning sunbed exposure and holidays with sun exposure. Analyses were performed to investigate the association between exposure to UV and melanoma prognostic factors. Between December 2010 and December 2013, information was obtained on 2,738 melanoma patients from 38 geographically representative Italian sites. A total of 49% of the patients were >55 years old, 51% were men, 50% lived in the north of Italy and 57% possessed a high level of education (at least high school). A total of 8 patients had a family history of melanoma and 56% had a fair phenotype (Fitzpatrick skin type I or II). Of the total patients, 29% had been diagnosed with melanoma by a dermatologist; 29% of patients presented with a very thick melanoma (Breslow thickness, >2 mm) and 25% with an ulcerated melanoma. In total, 1% of patients had distant metastases and 13% exhibited lymph node involvement. Holidays with sun exposure 5 years prior to CM diagnosis were significantly associated with positive prognostic factors, including lower Breslow thickness (P<0.001) and absence of ulceration (P=0.009), following multiple adjustments for factors such as sociodemographic status, speciality of doctor performing the diagnosis and season of diagnosis. Sunbed exposure and sun exposure during peak hours of sunlight were not significantly associated with Breslow thickness and ulceration. Holidays with sun exposure were associated with favorable CM prognostic factors, whereas no association was identified between sunbed use and sun exposure during peak hours of sunlight with favorable CM prognostic factors. However, the results of the present study do not prove a direct causal effect of sun exposure on melanoma prognosis, as additional confounding factors, including vitamin D serum levels, may have a role.

The role of spectrophotometry in the diagnosis of melanoma

BackgroundSpectrophotometry (SPT) could represent a promising technique for the diagnosis of cutaneous melanoma (CM) at earlier stages of the disease. Starting from our experience, we further assessed the role of SPT in CM early detection.MethodsDuring a health campaign for malignant melanoma at National Cancer Institute of Naples, we identified a subset of 54 lesions to be addressed to surgical excision and histological examination. Before surgery, all patients were investigated by clinical and epiluminescence microscopy (ELM) screenings; selected lesions underwent spectrophotometer analysis. For SPT, we used a video spectrophotometer imaging system (Spectroshade® MHT S.p.A., Verona, Italy).ResultsAmong the 54 patients harbouring cutaneous pigmented lesions, we performed comparison between results from the SPT screening and the histological diagnoses as well as evaluation of both sensitivity and specificity in detecting CM using either SPT or conventional approaches. For all pigmented lesions, agreement between histology and SPT classification was 57.4%. The sensitivity and specificity of SPT in detecting melanoma were 66.6% and 76.2%, respectively.ConclusionsAlthough SPT is still considered as a valuable diagnostic tool for CM, its low accuracy, sensitivity, and specificity represent the main hamper for the introduction of such a methodology in clinical practice. Dermoscopy remains the best diagnostic tool for the preoperative diagnosis of pigmented skin lesions.

Immunoscore: a new possible approach for melanoma classification

Meeting abstracts Increasing evidence has supported the hypothesis that cancer development is influenced by the host immune system. The number, type and location of the immune cells infiltrating the tumor microenvironment (TILs) may either limit or promote tumor progression [[1][1]]. These

Dermoscopic diagnosis of amelanotic/hypomelanotic melanoma

Amelanotic/hypomelanotic melanoma (AHM) is a subtype including melanomas with little or no melanin pigmentation, amelanotic melanoma (AM); it represents 2-8 % of all melanomas.1-2 AM may be difficult to diagnose because of lack of pigmentation and symmetry: recently, germline mutations have been reported in the MC1R gene and to a certain extent also in the MITF gene.3 This article is protected by copyright. All rights reserved.

PSS3 EPIDEMIOLOGY, COSTS AND QUALITY OF LIFE IN PATIENT WITH SEVERE CHRONIC HAND ECZEMA

PND47 APPLICATION OF THE KANO METHODOLOGY FOR EVALUATING MIGRAINE TREATMENT EXPECTATIONS AMONG PATIENTS TREATED BY NEUROLOGISTS IN SPAIN: THE MIGREXX STUDY Matias J, Nocea G, Caloto T Hospital Universitario San Carlos, Madrid, Spain; Merck Sharp & Dohme, SA, Madrid, Spain OBJECTIVES: To classify the characteristics and properties of the pharmacological treatments among migraine patients treated by neurologists in Spain. Patients are becoming increasingly implicated in treatment decisions. Expectations in relation to therapy largely condition satisfaction with the results obtained. METHODS: Multicenter, cross-sectional study in adult patients with at least one prescription of antimigraine drugs within the last year. The protocol was approved by the CREC of La Princesa University Hospital (Madrid). Sociodemographic, and clinical characteristics of patients, as well as questions regarding their expectations with regard to migraine treatments and evaluation of the importance of their attributes are documented. Using a treatment expectations questionnaire and applying Kano methodology, sixteen treatment attributes were classifi ed as: Must-be, One-dimensional, Attractive, Indifferent, Reverse or Questionable. Patients were required to give informed consent. RESULTS: 68 neurologists included 174 patients diagnosed with migraine (mean age 39 years; 75% women). None of the attributes were considered “Must-be”. The attributes considered by most patients to be “One-dimensional” were the absence of long-term adverse effects (55%), to allow work/study activities (50%), to allow social and family relationship (50%), achievement of symptoms relief (47%) and pain relief (44.3%). The attributes considered “Attractive” by most patients were: achievement of rapid symptoms and pain relief (54%), and achievement of total disappearance of the pain (53.4%). The attributes that led to a greater dissatisfaction were the occurrence of long-term adverse effects, not to allow work activity or studies and not to achieve pain relief. The three attributes that led to a greater satisfaction were achievement of total disappearance of the symptoms and the pain, and rapid pain relief. CONCLUSIONS: The expectations regarding a medical treatment signifi cantly infl uence the satisfaction reached with the outcome of such treatment. a better knowledge of patient’s expectations can lead to a greater satisfaction associated with treatment outcomes.