Melanoma in children, adolescents, and young adults: a clinical pathological study in a Brazilian population.

Malignant melanoma in children, adolescents, and young adults is unusual, especially before puberty. In children (age, 0-14 years), most primary lesions are thick and atypical (amelanotic, simulating pyogenic granuloma). In the population of adolescents and young adults (age, 15-39 years), melanoma is the third most common cancer, only behind lymphoma and breast cancer. Our study investigated the records of 89 patients diagnosed with cutaneous melanoma at age 0-39 years at Hospital das Clínicas, Medical School, University of São Paulo between 1992 and 2002. They were divided into group A (0-14 years of age) and group B (15-39 years of age). The histopathology of all cases was reexamined. Statistical analysis of the data presented was performed, and the obtained data were compared with the literature. The frequency of melanoma in the group aged 15-39 years was higher in women, and the most affected site was the trunk. Additionally, melanomas were more frequent at an earlier age in patients with family history of melanoma (P = 0.014). Most cases were diagnosed, at histopathology, as superficial spreading melanoma. Thick nodular melanomas with Breslow values higher than 2 mm were associated with lymph node metastasis (P < 0.05). Our study revealed that melanoma in children, adolescents, and young adults may present peculiar behavior and outcome, which might reflect the genetic and yet not fully unraveled pathogenesis of this complex disease.

Analysis of the dermoscopic features of excised melanomas and their relation with tumor thickness in a tertiary hospital in Brazil.

BACKGROUND: Dermoscopy is a non-invasive, cost-effective tool useful in the assessment of pigmented lesions. The aim of this study was to analyze the dermoscopic features in excised melanomas in a tertiary hospital in Brazil and the influence of Breslow thickness on the dermoscopic features observed. METHODS: An observational, cross-sectional study in which dermoscopic images of 43 melanomas were evaluated. The patients were divided into three groups: in situ, thin invasive melanoma (Breslow thickness <1 mm), and thick invasive melanoma (Breslow thickness ≥1 mm). RESULTS: We studied 33 patients with 43 melanomas. Twenty-one (48.8%) were melanoma in situ, 16 (37.2%) were thin melanomas, and 6 (14%) were thick melanomas. The most frequent dermoscopic criteria observed in all cases were atypical pigment network, multiple colors (3 or more), asymmetrical blotches, and peripheral asymmetric dots and globules. There was a statistically significant difference in the three groups regarding the frequency of atypical vessels, white scar areas, blue-white veil, shiny white structures, and radial streaming. The group of invasive melanomas presented with a higher frequency and statistical significance (P < 0.05) of atypical vessels, white scar areas, blue-white veil, and shiny white structures when compared to in situ melanomas. The presence of radial streaming and blue-white veil was more frequent in thick invasive melanomas than in thin invasive melanomas. The presence of a higher number of structures was seen in invasive melanomas, with a median of 5 and 7.5 structures for thin and thick invasive tumors, respectively. CONCLUSIONS: In line with prior data, we identified an association between invasive melanomas and structures linked to fibrosis and tumor vascularity. Specifically, we noted the presence of atypical vessels, scar-like white areas, a blue-white veil, and shiny white structures. Also, a higher number of dermoscopic structures was seen in invasive melanomas. In thicker melanomas, we observed additional findings, including a higher frequency of radial streaming and a blue-white veil.

DNA damage and repair in leukocytes of melanoma patients exposed in vitro to cisplatin.

Resistance to chemotherapeutic drugs can be an obstacle to a successful treatment of cancer patients in part associated with individual response and differences in the DNA repair system. The Comet assay is an informative test to investigate DNA damage and repair in cells in response to a variety of DNA-damaging agents, including chemotherapeutic drugs. The aim of this study was to assess leukocytes damage after in-vitro cisplatin treatment and DNA repair action using the Comet assay in 20 patients with melanoma and 20 cancer-free individuals. Leukocytes' DNA damage before and after cisplatin treatment, in three different concentrations, was analyzed. The DNA repair capability was investigated after 1-5 h of in-vitro cells growing without cisplatin. The Comet score of the patients' basal DNA damage was higher than that observed in controls, but the difference was not statistically significant (P=0.85). Although both groups had similar Comet scores to all cisplatin concentrations tested and the DNA repair times, the basal DNA damage (P<0.001) and cisplatin damages (P<0.005) were statistically lower than the different repair times investigated. Considering the progressive increase in the Comet score due to repair time, the negative results here observed could be associated with the reduced cell culture incubation that should be better evaluated. Considering the mutagenic action of cisplatin on tumor cells and the importance of individual DNA repair mechanisms in the chemotherapeutic melanoma treatment, the peripheral leukocytes could be particularly useful as a tool for DNA repair response identified by the Comet assay.

PTCH1 gene mutations in exon 17 and loss of heterozygosity on D9S180 microsatellite in sporadic and inherited human basal cell carcinomas.

BACKGROUND: Basal cell carcinomas (BCCs) are the most frequent human cancer that results from malignant transformation of basal cells in the epidermis. Gorlin syndrome is a rare inherited autosomal dominant disease that predisposes with multiple BCCs and other birth defects. Both sporadic and inherited BCCs are associated with mutations in the tumor suppressor gene PTCH1, but there is still uncertainty on the role of its homolog PTCH2. OBJECTIVES: To search for mutations and genomic instability in sporadic and inherited BCCs. METHODS: DNA obtained from leukocytes and tumor cells was amplified by polymerase chain reaction regarding five exons of PTCH1 and PTCH2 and neighboring microsatellites. Exons were sequenced and compared with the GenBank database. RESULTS: Only D9S180, of six microsatellites, showed loss of heterozygosity in three BCCs (two sporadic and one inherited). One sporadic BCC presented the mutation g.2885G>C in exon 17 of PTCH1, which predicts the substitution p.R962T in an external domain of the protein. In addition, the leukocytes and tumor cells of one patient with Gorlin syndrome showed the mutation g.2839T>G in the same exon and gene, which predicts a p.E947stop and truncated protein. All control and tumor samples presented IVS9 + 217T in intron 9 of PTCH1. CONCLUSION: Mutations found in the PTCH1 gene and neighboring repetitive sequences may have contributed to the development of the studied BCCs.

Association of p53 arginine polymorphism with skin cancer.

BACKGROUND: The presence of arginine at codon 72 in p53 protein is proposed to be a genetic risk factor in human papillomavirus (HPV)-related carcinogenesis. OBJECTIVE: To study the prevalence of p53 polymorphism at codon 72 in skin biopsies of epidermodysplasia verruciformis (EV) patients compared to DNA samples from healthy individuals. PATIENTS AND METHODS: DNA samples extracted from normal skin and tumor biopsies of 22 Brazilian patients with EV and blood samples from 27 healthy Brazilian individuals were studied for p53 codon 72 polymorphisms using restriction fragment length polymorphism (RFLP) analysis. RESULTS: All EV patients with the malignant form of EV were homozygous for arginine (Arg/Arg) at codon 72 of the p53 gene, in contrast to none with the benign form (P < 0.0001). CONCLUSIONS: p53 arginine polymorphism is likely to be associated with the development of skin malignancies in EV patients from Brazil.

PTCH1 gene mutations in exon 17 and loss of heterozygosity on D9S180 microsatellite in sporadic and inherited human basal cell carcinomas

Basal cell carcinomas (BCCs) are the most frequent human cancer thatresults from malignant transformation of basal cells in the epidermis. Gorlin syndrome is a rare inherited autosomal dominant disease that predisposes with multiple BCCs and other birth defects. Both sporadic and inherited BCCs are associated with mutations in the tumor suppressor gene PTCH1, but there is still uncertainty on the role of its homolog PTCH2.