Suppression of melanoma cell proliferation by histidine decarboxylase specific antisense oligonucleotides.

Histidine decarboxylase (HDC) is expressed by the cells of melanoma, in which the histamine content tends to be relatively high. This study shows that elevated expression of HDC was found by western blot analysis of primary and metastatic melanoma tissue using a polyclonal HDC specific antibody. The specificity of anti-HDC antibody was confirmed by inhibition of HDC translation (i.e., immunopositivity) in melanoma cells by HDC-specific antisense oligonucleotide. Moreover, the decrease in proliferation caused by HDC antisense oligonucleotides indicates considerable functional relevance of histamine synthesis in melanoma growth and suggests a possible in situ application of specific antisense oligonucleotides for HDC in melanoma therapy.

Expression of CD44v3 splice variant is associated with the visceral metastatic phenotype of human melanoma.

We analyzed the immunohistochemical expression of the metastasis-associated protein, CD44v3, in 46 primary human malignant melanomas (MMs). This is the first time that the v3 splice variant of CD44 was found to be expressed in human melanomas (15 of 46), ranging from 3% to 35% of the cell population in the positive tumors. The expression of CD44v3 was observed in tumors thicker than 1.0 mm, and one-third of these tumors proved to be positive irrespective of the thickness. Patients were followed for a minimum of 61 months. The onset of lymph node or organ metastases occurred not later than 58 months and 60 months, respectively. Of the 15 CD44v3 positive tumors, 14 were observed in the organ metastatic tumor group, comprising the majority of those cases (14 of 21), and this association proved to be statistically significant compared with the non-metastatic (P<0.05) and lymph-node metastatic cases (P<0.01). CD44v3 expression in melanoma was also confirmed at the protein and messenger (mRNA) level in several human melanoma cell lines using flow cytometry and reverse transcriptase polymerase chain reaction analysis. In parallel to CD44v3, MMP-2 expression (determined using immunohistochemistry) was significantly elevated (P<0.05) but only in the organ metastatic group of MM. The 5-year survival of patients having thicker tumors than 1.0 mm (where v3 expression occurred) who had CD44v3+ tumors was significantly lower than those of the negative ones (35.7% versus 68.2%, respectively; P=0.025). Finally, we observed that the CD44v3-expressing tumors were characterized by significantly higher MMP-2 expression than the CD44v3-negative tumors (P<0.001), indicating a possible correlation between CD44v3- and MMP-2-positive phenotype and the organ metastatic potential of MM.

Porokeratosis plantaris, palmaris, et disseminata.

A 58-year-old man and his son presented with the clinical and histologic characteristics of porokeratosis plantaris, palmaris, et disseminata. Porokeratosis plantaris, palmaris, et disseminata also occurred in two other family members. Marked improvement was demonstrated with oral aromatic retinoid (Tigason) therapy. The differential diagnosis from the other types of porokeratosis is discussed. It is suggested that punctate porokeratosis is a form fruste of porokeratosis plantaris, palmaris, et disseminata.

The loss of NM23 protein in malignant melanoma predicts lymphatic spread without affecting survival.

NM23 is considered to be a metastasis suppressor gene the role of which as prognosticator in the case of malignant skin melanoma (MM) is highly controversial due to different results on gene, and protein expressions. Accordingly, we analyzed the protein expression of NM23 in 32 primary skin melanomas with a follow-up period of 5 years minimum. We found that NM23 expression was the lowest in the thickest primary tumors (based on the % of the positive cells and the incidence of low expressor tumors) but the difference was not significant statistically due to the extreme heterogeneity of the tumors. When primary tumors were grouped according to their biological behavior (non-metastatic; lymph-node (LN) metastatic; organ and LN metastatic tumors) we observed that the lowest NM23 protein expression (based on the % of positive tumor cells as well as on the incidence of low expressor tumors) was found in the LN metastatic tumors compared to other groups (p < 0.05). The NM23 phenotype of the primary tumors remained stable in the corresponding LN metastases in the case of the 5 analyzed tumors. There was no difference in the 5-year survival between patients with low (< 50% positive cells) or high NM23 protein expressing primary tumors. Collectively, these data suggest that the NM23 protein expression in the primary tumors of MM predicted lymphatic spread but did not affect 5-year survival because it did not correlate with organ metastasis.

[Prognosis and invasion marker expression of cutaneous melanoma. Metastasis-associated genes (nm23, CD44v3, MMP2]. / A cutan melanoma prognózisa és inváziós marker expressziója. Metasztázis asszociált gének (nm23, CD44v3, MMP2).

For the evaluation of the prognosis of the melanoma malignum (MM) several markers have been used before but none of them was powerful enough therefore a search for new markers is justified. The authors have studied the expression of three metastasis associated proteins, nm23, CD44v3 and MMP2 collagenase using immunohistochemistry on the paraffin embedded tissue samples of 22 primary skin melanomas. The expression of these markers was independent from the thickness of the tumor or the clinical stage of the disease. Due to the frequent discrepancy between the thickness of the tumor and the actual outcome of the disease, they regrouped the cases according to the biological behaviour of the tumor into non-metastatic, lymph node-metastatic and organ metastatic forms. Based on the MMP2 expression +/- tumors can be found but the expression does not correspond to the biological behaviour of MM while decreased nm23 expression characterized the lymph node metastatic tumors. CD44v3 expression was rare in MM and occurred at low level, however, when expressed it showed significant correlation to the organ metastatic phenotype. The authors concluded that the classic invasion markers in case of MM have a limited potential in the characterisation of the invasive phenotype, therefore more sensitive markers are necessary.

[Interferon-alpha and PUVA therapy for mycosis fungoides]. / Mycosis fungoides interferon-alfa- és PUVA-kezelése.

14 patients suffering from early stage mycosis fungoides were treated with interferon alpha 2-a and PUVA/1 patient in stage I a, 3 patients in stage I b, 4 patients in stage II a and 6 patients in stage II b/during 3-21 months time course. Interferon alpha 2-a was administered 3 times a week, in escalating dose from 3 MU to 9 MU, determining the individual maximal tolerated dose. All of the patients responded well to the treatment. Partial remission was observed after 4-13 weeks of treatment. Total remission developed in 8 cases, after 8 weeks- 9 months of the treatment. Side effects occurred frequently: weight loss, pain, fever, fatigue, leucopenia, thrombopenia, liver enzyme elevation. Because of the side effects the dose of the interferon was reduced individually, the dose reduction did not cause relapse.

[Use of interferon-alpha (IFN-alpha) in the treatment of keratoacanthoma]. / Die Anwendung von Interferon alpha (IFN alpha) in der Keratoakanthombehandlung.

BACKGROUND AND OBJECTIVE: Keratoacanthoma are benign epithelial tumors. The aim of this study was to determine the effects of interferon alpha on keratoacanthoma. PATIENTS/METHODS: Six patients presented with histologically proven keratoacanthoma which were large or otherwise difficult to excise. Intra and perilesional interferon-alpha treatment with 3 million IU weekly was started. RESULTS: In 6-15 weeks all tumors were cured. CONCLUSIONS: Treatment with intralesional interferon-alpha offers a new possibility in cases of large keratoacanthomas, or those which are not surgically excisable.

[Multiple clear cell acanthomas]. / Multiple Klarzellakanthome.

Multiple clear cell acanthomas were observed on the legs of a 77-year-old male patient. Some of the tumors showed a tendency to aggregate in a circumscribed area on his right lower leg. The multiple occurrence of these benign epidermal tumors is extremely rare; moreover, there has not been observed any tendency to aggregation so far.

Exacerbation of paraneoplastic pemphigus by cyclophosphamide treatment: detection of novel autoantigens and bronchial autoantibodies.

A 48-year-old woman with a follicular, grade III, B-cell non-Hodgkin lymphoma developed clinical, immunopathological and histological features of paraneoplastic pemphigus. The skin symptoms flared after repeated cyclophosphamide infusions, and were preceded and accompanied by a progressive dyspnoea. Although the skin and oral mucosal disease went into remission with high-dose steroid and intravenous immunoglobulin therapy, the severe alveolitis led to death. Immunoblotting of human epidermal extracts showed that the patient's serum IgG reacted with the 210-kDa envoplakin, 190-kDa periplakin, as well as the recombinant protein of BP180 NC16a domain. IgG and IgA enzyme-linked immunosorbent assays for desmoglein 3 were positive, too. Indirect immunofluorescence studies on COS-7 cells transiently transfected with desmocollin 1-3 cDNAs showed that the patient's serum contained IgG and IgA antibodies to desmocollin 3 as well as IgG antibodies to desmocollin 2. Serum IgG and IgA strongly stained rat bronchial epithelium, corresponding to autoantibodies possibly involved in the pathomechanism of the severe lung disease. In this case, which was characterized by a mixed IgA/IgG antibody panel displaying known and unique antigenicity, the serious episodes of paraneoplastic pemphigus flared after cyclophosphamide treatment.