RESUMO
The detoxifying enzyme glutathione-s-transferase pi (GST-π) is present in keratinocytes and melanocytes and exerts a protective role against tumour progression. Melanomas close to melanocytic naevus remnants occur less frequently on sun-exposed areas, whereas solar dermal elastosis, hallmark of chronic sun-damage, characterise melanomas on sun-exposed skin. We evaluated the expression of GST-π in 113 melanomas associated to melanocytic naevus remnants or to solar dermal elastosis, classified according to clinical characteristics, history of sun exposure, histological subtypes and AJCC staging. Chronically sun-damaged melanomas, identified by moderate-severe solar dermal elastosis, showed a lower nuclear GST-π expression and a higher thickness than those related to melanocytic naevus remnants (p < 0.03). Multivariate logistic regression analysis demonstrated that male gender and chronic sun-exposure are independent risk factors significantly associated to melanomas localised on the trunk (OR = 3.36, 95% CI: 1.31-8.65; OR = 5.97, 95% CI: 1.71-20.87). If confirmed on a larger series, lower expression of nuclear GST-π in melanoma cells could represent a possible marker of chronically sun-damaged melanoma pathogenesis.
Assuntos
Biomarcadores Tumorais/análise , Glutationa S-Transferase pi/análise , Melanoma/enzimologia , Melanoma/epidemiologia , Neoplasias Induzidas por Radiação/enzimologia , Neoplasias Induzidas por Radiação/epidemiologia , Nevo Pigmentado/enzimologia , Nevo Pigmentado/epidemiologia , Luz Solar/efeitos adversos , Adulto , Idoso , Biópsia , Distribuição de Qui-Quadrado , Regulação para Baixo , Feminino , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Itália/epidemiologia , Modelos Logísticos , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Neoplasias Induzidas por Radiação/patologia , Nevo Pigmentado/patologia , Razão de Chances , Fatores de Risco , Fatores Sexuais , Fatores de TempoRESUMO
BACKGROUND: Chronic myeloid leukemia (CML) is a myeloproliferative disorder primarily characterized by the presence of the Philadelphia chromosome resulting from a reciprocal translocation between the long arms of chromosomes 9 and 22. This translocation determines a fusion gene, bcr-abl, which encodes a constitutively active protein, tyrosine kinase, resulting in decreased apoptosis, defective adhesion, and genomic instability in transformed cells. The tyrosine kinase activity and its effects represent a potential pharmacologic target of tyrosine kinase inhibitors, such as imatinib. Flare of Kaposi's sarcoma (KS) is well described in immunosuppressed patients treated with corticosteroids and rituximab, but has not yet been reported during treatment with imatinib. OBJECTIVE: We report a case of cutaneous KS lesions in a patient affected by CML treated with imatinib. CASE SUMMARY: A 61-year-old white male patient (weight, 90 kg) was diagnosed with CML in March 2006 at the Division of Hematology, University of Rome "Tor Vergata," Rome, Italy. He was treated with imatinib 400 mg/d, which improved his general condition with few adverse effects. After 12 months of treatment, molecular biology showed an important reduction in the peripheral blood of the fusion oncoprotein bcr-abl p210-b3a2. However, at the same time, multiple cutaneous violaceous papular-nodular lesions appeared on his left forearm. A punch biopsy showed the presence of KS, whereas a polymerase chain reaction assay documented the presence of human herpes virus type 8 (HHV8) DNA in the skin lesion. Serologic HIV was negative and HHV8 viremia was under the limit of quantitation of the assay. Total body computed tomography scan did not reveal any mucosal or visceral lesion. CONCLUSIONS: We present a case of a patient with CML who developed KS 12 months after starting treatment with imatinib 400 mg/d. The mechanism behind the development of the cutaneous lesions is unclear, and could have either a casual clinical association or be related to the study drug. According to the Naranjo adverse drug reaction probability scale, the development of KS in this case was probably associated with the imatinib treatment (score, 5-8).
Assuntos
Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Piperazinas/efeitos adversos , Piperazinas/uso terapêutico , Pirimidinas/efeitos adversos , Pirimidinas/uso terapêutico , Sarcoma de Kaposi/complicações , Corticosteroides/uso terapêutico , Benzamidas , DNA Viral/análise , Proteínas de Fusão bcr-abl/metabolismo , Soronegatividade para HIV , Herpesvirus Humano 8/genética , Humanos , Mesilato de Imatinib , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Sarcoma de Kaposi/patologia , Pele/patologiaRESUMO
Nail psoriasis occurs in 7% to 40% of children, with a similar pattern of clinical presentation to that of adults. In 0.6% to 2.3% of the patients nail changes appear as the only sign of the disease, preceding other skin and articular involvement. No pediatric clinical trials are available yet, but considering the successful use of tazarotene for nail dystrophy therapy in adults, we chose this drug to treat a child.