Marked genetic differences between BRAF and NRAS mutated primary melanomas as revealed by array comparative genomic hybridization.

Somatic mutations of BRAF and NRAS oncogenes are thought to be among the first steps in melanoma initiation, but these mutations alone are insufficient to cause tumor progression. Our group studied the distinct genomic imbalances of primary melanomas harboring different BRAF or NRAS genotypes. We also aimed to highlight regions of change commonly seen together in different melanoma subgroups.

Prognostic relevance of the expressions of CAV1 and TES genes on 7q31 in melanoma.

The 7q31 locus contains several genes affected in cancer progression. Although evidences exist regarding its impact on tumorigenesis, the role of genetic alterations and the expressions of locus-related genes are still controversial. Our study aimed to define the 7q31 copy number alterations in primary melanomas, primary-metastatic tumor pairs and cell lines.

Characterization of candidate gene copy number alterations in the 11q13 region along with BRAF and NRAS mutations in human melanoma.

Amplification of the 11q13 chromosomal region is a common event in primary melanomas. Several candidate genes are localized at this sequence; however, their role in melanoma has not been clearly defined. The aim of this study was to develop an accurate method for determining the amplification pattern of six candidate genes that map to this amplicon core and to elucidate the possible relationship between BRAF, NRAS mutations and CCND1 copy number alterations, all of which are key components of the MAP kinase pathway.

Characterization of 9p21 copy number alterations in human melanoma by fluorescence in situ hybridization.

Alteration of the CDKN2A (alias p16) tumor suppressor gene, located on 9p21, occurs frequently in familial and sporadic melanomas. Beside CDKN2A, other genes (e.g.

EGFR gene copy number alterations in primary cutaneous malignant melanomas are associated with poor prognosis.

Copy number alterations of the epidermal growth factor receptor (EGFR) gene have been extensively analyzed in different cancers, but no data are available for primary malignant melanoma. The aim of the present study was to simultaneously investigate the EGFR gene and chromosome 7 copy number alterations in 81 cutaneous malignant melanomas by interphase FISH and correlate the data with clinicopathological parameters of patients. EGFR mRNA levels were detected by Affymetrix GeneChip Human Genome U133 Plus 2.

Extra copies of c-myc are more pronounced in nodular melanomas than in superficial spreading melanomas as revealed by fluorescence in situ hybridisation.

Background: Amplification of c-myc is a common genetic alteration and associated with a poor prognosis in a variety of cancers. Extra copies of the gene have been found in large numbers of melanoma metastases, but only few primary tumours have been studied. We investigated the c-myc copy number alterations in two different subtypes of primary melanomas with different biological behaviours.

Immunohistochemical examination of P-cadherin in bullous and acantholytic skin diseases.

Autoimmune blistering diseases (pemphigus vulgaris, pemphigus foliaceus, bullous pemphigoid, dermatitis herpetiformis) and certain genodermatoses with acantholysis (Darier-disease, Hailey-Hailey disease) have different aetiological factors, but all result in bulla formation and/or in acantholysis. Cadherins are Ca++-dependent cell-cell adhesion molecules which play an important role in the cellular connection between normal cells. P-cadherin is involved in the selective adhesion of epidermal cells, and is expressed only on the surfaces of the two basal layers.

[The role of PET scan in the diagnosis of malignant melanoma].

Comprehensive, accurate staging has a critical role in planning rational treatment strategies for patients with malignant melanoma (MM). In the present study the authors investigate the value of FDG PET in staging and restaging based on the investigation of 37 high-risk MM patients and compare the results with the one obtained by conventional imaging techniques (X-ray, US, CT, MR and bone scan). Thirty-nine whole body PET scans were carried out.

Chromosomal imbalances in primary and metastatic melanomas revealed by comparative genomic hybridization.

Characteristic genetic changes underlying the metastatic progression of malignant melanoma is incompletely understood. The goal of our study was to explore specific chromosomal alterations associated with the aggressive behavior of this neoplasm. Comparative genomic hybridization was performed to screen and compare genomic imbalances present in primary and metastatic melanomas.

Prevalence and age distribution of human herpesvirus-8 specific antibodies in Hungarian blood donors.

Sera of blood donors were investigated by a peptide ELISA and indirect immunofluorescence assay to assess the prevalence of HHV-8 infection in the Hungarian population. A 14 amino acid long synthetic oligopeptide from the carboxyterminus of orf65/small virus capsid antigen was used as antigen in the ELISA. ELISA results were confirmed by recombinant orf65 antigen Western blot.

HHV-8 ELISA based on a one-step affinity capture of biotinylated K8.1 antigen.

The immunogenic envelope antigen gp35-37 of human herpesvirus-8 (HHV-8) is encoded by orfK8.1. An ELISA is described using streptavidin capture of bacterially expressed and biotinylated recombinant K8.

Involvement of chromosome losses in the progression and metastasis formation of a human malignant melanoma.

To characterize the possible cytogenetic link between a primary tumor and its metastasis, interphase cytogenetic analysis was performed on tumor cells and cutaneous metastasis from a male patient with malignant melanoma by using fluorescence in situ hybridization. The numbers of distinct hybridization domains specific for ten different pericentromeric sequences were used as indicators of copy numbers of these chromosomes. In the primary tumor, the majority of cells had two copies of these chromosomes, but significant numbers of nuclei also were present with one and three copies.

bcl-2 vs p53 protein expression and apoptotic rate in human nonmelanoma skin cancers.

Background: A failure in the apoptotic response after severe genomic damage could facilitate cell transformation and tumor development, and a constitutive overexpression of either p53 or bcl-2 protein in nonapoptotic tumor cells could signify a defective bax-mediated apoptosis.

Objectives: To investigate whether a negative correlation occurs between these 2 proteins in nonmelanoma skin cancer and whether overexpression of either protein is associated with a low rate of spontaneous apoptosis.

Design: Immunohistochemical study of nonmelanoma skin cancer archive material.

Erythema Gyratum Repens an Immunological Paraneoplastic Dermatosis.

The authors present a patient with erythema gyratum repens who had a bronchogenic carcinoma. Autoantibodies and complement at the basement membrane zone of the skin was found which suggest that erythema gyratum repens may have an immunological pathogenesis but the nature of the antigen should be further characterised.

Expression of thrombospondin-1 (TSP1) and its receptor (CD36) in healthy and diseased human skin.

In the present study, an analysis was made of the expression pattern of thrombospondin-1 (TSP1) and its receptor (CD36) in skin biopsies obtained from healthy volunteers and from patients with lichen planus, lupus erythematosus, cutaneous T-cell lymphoma and psoriasis vulgaris. Using monoclonal antibodies against TSP1 in biopsies from the healthy volunteers and from both clinically involved and uninvolved skin of the patients, a specific peroxidase-positive reaction was detected around the sweat glands in the dermis. In all cases investigated, the CD36-positive lesional keratinocytes remained TSP1-negative.

Hypertrichosis lanuginosa acquisita.

Hypertrichosis lanuginosa acquisita was observed in a female patient with stage IV malignant melanoma and also diffuse melanosis of the skin. The patient died within 2 months after the appearance of HL.

[Melanoma screening in Debrecen].

Melanoma screening examination has been organized in Debrecen. The aid of it is the early detection and treatment of melanoma. Different methods (educational pamphlet, postgradual training of GP's, TV, radio) help the work of dermatologists.

[Forme fruste of Hunter's disease].

We report on a 19-year-old girl with hepatosplenomegaly and possible hematological disease. We suspected Gaucher's disease on account of histological and biochemical evidence found in specimens from the liver, spleen, and bone marrow. 18 months later, pebbled skin developed on her neck and upper back.

A study on cell-mediated immunity in polymorphic light eruption.

Polymorphic light eruption (PLE) can be defined as a delayed abnormal response to sunlight. In this paper some features of the presumable immune response were studied in 55 patients with PLE and the results were compared with the findings available in 58 cases with porphyria cutanea tarda (PCT). The mean intracutaneous reactivity index measured by skin tests of delayed type was normal in both diseases.

Immunopharmacologic properties of WY-16, 922, a new orally effective antiallergic agent.

In a series of tests designed to illustrate immune reactions similar to those obtained in atopic disease, Wy-16,922 effectively inhibited reaginic-mediated immunologic reactions in the skin, lungs and mast cell. It was found to be devoid of immunosuppressant, antimediator, anti-inflammatory, steroid or bronchodilator properties as well as acute toxicity. Although the mechanism of action of Wy-16,922 is unknown, it appears to limit the release (not the effects) of allergic mediators in a manner similar to that described for disodium cromoglycate.

Immunopharmacologic properties of WY-16,922, a new orally effective antiallergic agent.

In a series of tests designed to illustrate immune reactions similar to those obtained in atopic disease, Wy-16,922 effectively inhibited reaginic-mediated immunologic reactions in the skin, longs and mast cell. It was found to be devoid of immunosuppressant, antimediator, anti-inflammatory, steroid or bronchodilator properties as well as acute toxicity. Although the mechanism of action Wy-16,922 is unknown, it appears to limit the release (not the effects) of allergic mediators in a manner similar to that described for disodium cromoglycate.

Oxanilic acids, a new series of orally active antiallergic agents.

A large number of oxanilic acid esters and N-heteroaryl oxamic acid esters were prepared and found to have antiallergic activity using the rat passive cutaneous anaphylaxis (PCA) test. Many of the oxanilic acid esters are active orally, with the most active species having an aryl 2'-carbamoyl group and a 3'-methoxy group. Hydrolysis of the ester from the oxanilic ester moiety causes a loss of oral activity.