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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. [ABSTRACT FROM AUTHOR]

Background: The possible correlation between melanoma and Parkinson's disease (PD) has been intensively studied. In this work, we aimed to assess the coincidence of skin malignancies and PD at a dermato-oncological university centre in Central-Eastern Europe, Hungary., Methods: From 2004 to 2017, a retrospective analysis of the centre's database was performed based on International Statistical Classification of Diseases-10 codes., Results: Out of the patients who visited the clinic during the study period, 20,658 were treated for malignant skin tumours. Over the 14 years, 205 dermatological patients had PD simultaneously, 111 (54%) of whom had at least one type of skin malignancy: melanoma (n=22), basal cell carcinoma (BCC) (n=82), or squamous cell carcinoma (SCC) (n=36) (in some patients, multiple skin tumours were identified). Compared to the age- and sex-matched control group, patients with PD had a significantly lower risk for basal cell carcinoma (OR, 0.65; 95% CI, 0.47-0.89, p=0.0076) and for all skin tumours (OR, 0.74; 95% CI, 0.56-0.98, p=0.0392) but not for melanoma., Conclusions: We found a decreased risk of all skin tumours and basal cell carcinoma and an unchanged risk of melanoma among patients with PD. However, it should be kept in mind that some large-scale meta-analyses suggest a higher incidence of melanoma after a diagnosis of PD, indicating the importance of skin examination in this vulnerable population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tóth, Diakoumakou, Kuroli, Tóth, Kuzmanovszki, Szakonyi, Lőrincz, Somlai, Kárpáti and Holló.)

High endothelial venules (HEVs) are specialized vessels in lymphoid organs, supporting lymphocyte trafficking from the blood. As the presence of these vessels was described recently in tumors, it was proposed that they could facilitate the development of antitumor immune response, resulting in improved prognosis. The aim of our study was to analyze the correlation of the density of HEVs with that of the different immune cell types as well as with the clinicopathologic parameters and the disease outcomes in patients with cutaneous melanoma. Primary melanoma samples of 118 patients were analyzed retrospectively by immunohistochemical labeling and quantitation of vessels stained with the MECA-79 antibody, as well as a panel of eight different immune cell types (CD8 and CD45RO T cells, lymphocytes expressing the CD25, CD134, or CD137 activation markers, FOXP3 regulatory T cells, CD20 B cells, and DC-LAMP mature dendritic cells). Correlations of MECA-79 vessel density with that of the immune cells, as well as with clinicopathologic parameters and disease outcomes were evaluated. We showed that the number of MECA-79 vessels correlates strongly with the peritumoral density of B and T lymphocytes. Moreover, higher HEV numbers were detected in tumors hosting tertiary lymphoid structures as well as in those of axial location compared with the ones in the extremity and in men compared with women, whereas no association was found with patient age, tumor thickness, histologic type or ulceration, or with the survival of melanoma patients. The density of MECA-79 HEVs in primary melanomas shows a correlation with B and T-lymphocyte density and differences according to the presence of tertiary lymphoid structures, tumor site, and the sex of the patient. However, it has no prognostic value.

Pregnancy associated melanoma (PAM) by definition appears during pregnancy or within 1 year after delivery. In this retrospective study we analysed the pathological characteristics and survival rate of PAM and matched the data with non-pregnant age- and stage-matched control patients. Between 2003 and 2014, 34 pregnant women (aged 32.5 ± 5.6 years) were diagnosed with melanoma at the Department of Dermatology, Venereology and Dermatooncology of the Semmelweis University. During the pathological process histologic subtype, Breslow thickness and Clark level, tumor cell type, mitotic rate, peritumoral inflammation, as well as ulceration, regression, necrosis, vascular invasion and presence of satellite were analyzed and related to clinical data. Primary tumor location and clinical staging, disease course, local recurrence and metastases, 5-year survival rate, other tumor development before or after the diagnosis of melanoma have also been documented. We found no difference in all parameters between pregnant and non-pregnant melanoma cases except peritumoral inflammation which was higher in PAM group, moreover the presence of mild inflammation was significantly higher in PAM group compared to non-pregnancy associated melanoma (NPAM) women group.

Ectopic lymphoid structures have been described in several tumor types including metastatic lesions, but not primary tumors, of patients with melanoma. Here we present evidence of B-cell follicles in primary cutaneous melanomas, being present in 39 of 147 cases (27 %). B-cell clusters were associated with T lymphocytes, most of which belonging to CD45RO(+) memory T cells. A network of CD21(+) follicular dendritic cells was demonstrated in 8 of 22 cases studied (36 %). MECA-79(+) HEV-like venules were observed in the neighborhood of the follicles in the majority of cases, however, their presence was not confined to tumors hosting ectopic lymphoid structures. The appearance of B-cell aggregates did not show association with the outcome of the disease, although a trend for their higher prevalence was observed in thicker tumors. Our results show that neogenesis of lymphoid structures does occur in primary melanomas, albeit with lower frequency compared to that reported in metastases.

Incidence of subsequent malignant tumor development in 740 patients with primary cutaneous melanoma verified between 2006 and 2010 at the Semmelweis University was studied retrospectively and was compared to data of sex and age matched Hungarian population. The follow-up period was 1499 person-years for the whole group from the diagnosis of index melanoma with an average of 2 years. Standardized incidence rate (SIR) was established as the ratio of observed and expected values. The risk of all subsequent malignancies was 15- and 10-fold higher in males (SIR: 15.42) and in females (SIR: 10.55) with melanoma, than in the general population. The increased cancer risk resulted mainly from the significantly higher skin tumor development: SIR values were 160.39 and 92.64 for additional invasive melanoma and 342.28 and 77.04 for subsequent in situ melanoma in males and females, respectively. Non-melanoma skin cancers also notably contributed to the higher risk, the SIR was elevated in both genders to the same extent (males: 17.12, females: 17.55). The risk was also significantly higher for extracutaneous tumor development like chronic lymphocytic leukemia, colon and kidney cancer (both genders), non-Hodgkin's lymphoma, cervical cancer (females), and bladder carcinoma (males). These data underline the importance of patient education and the necessity of frequent medical follow up, including a close-up dermatological screening of melanoma survivors for further malignancies.

Introduction: Survival of patients with malignant melanoma primarily depends on tumor stage. Hungarian National Cancer Registry does not specify tumors according to TNM stages., Aim: The authors aimed to survey the stage distribution of melanomas at the Department of Dermatology, Dermatooncology and Venerology, Semmelweis University., Method: 1160 patients (558 males and 602 females, aged 60.5±16 and 57±17 years, respectively) diagnosed with cutaneous melanoma between 2004-2009 were included., Results: In comparison with international studies, the case distribution was favorable in stages IA and IV, i.e. the proportion of early melanomas was relatively high (IA: 43.8%), while the incidence in stage IV was low (0.4%). In stages IB-IIA the incidence was significantly lower, while in IIC, IIIA, IIIB it was higher as compared to published data from Western-Europe, Australia and the United States., Conclusions: The study underlines the necessity of prevention and awareness campaigns that may result in increase of early diagnosis of melanomas.

Pathological classification of malignant melanoma did not change in the past decade, it was just completed with UV-induced skin alterations. A new feature, however, is the establishment of molecular classification of melanoma indicating that beside the most frequent genetic alterations (BRAF, NRAS, CKIT mutations) there is a wide variety of rare molecular subclasses. Unfortunately, none of these genetic alterations can be used to discriminate benign lesions from malignant ones. The frequently used "melanoma" markers are mostly melanosomal markers, therefore they are not helpful for this diagnostic purpose either. More recently, novel FISH kits have been developed analyzing characteristic copy number alterations specific for malignant melanoma. Though melanosomal markers are helpful in differencial diagnostics, the presence of normal melanocytes in various tissues (lymph nodes, intestine or brain) requires application of molecular techniques when melanoma metastasis is in question.

The industrial use of the ionizing radiation (IR) particularly stresses the safe work, regular health control is inevitable. Since previous occupational cohorts reported contradictory data on the incidence of melanoma among nuclear industry workers, and in few publications significant increase of it has been described, our clinic was requested by the industry to screen malignant skin tumours among the workers of a power plant. Within a year we have investigated 556 workers, 275 females and 281 males. Out of them 283, majorly males had been officially confirmed as to be employed at hazardous, but strictly controlled environment for an average of 18 years (1-32 years). To distinguish between IR and environmental UV (UVA+UVB) induced cutaneous malignancies we determined the sun and tanning bed exposure of the workers. One in situ melanoma developed in a woman with type I skin, bullous sunburns in the history, who had worked in safe environment for 26 years. Basal cell carcinoma was identified in two men, each of them worked for more than 20 years with IR (in hazardous environment). One had type I skin, the other had type II skin. These results didn't differ significantly (chi-squared test; p = 0, 2437 and 1, 0) from the national population data and the results of Euromelanoma screening campaign in Hungary. Our data clearly show, that 1./UV exposure and skin type should be evaluated in occupation cohort studies. 2./The melanoma incidence was not significantly higher among the employees of the power plant than in the general Hungarian population, according to the results of our study, the only Hungarian power plant is safe as far as the skin carcinogenesis is concerned.

Studies on the prognostic importance of tumor-infiltrating lymphocytes have mainly focused on T cells, while little is known about the role of tumor-infiltrating B lymphocytes. We investigated the prevalence of CD20(+) B cells by immunohistochemistry in primary melanoma samples of 106 patients and analyzed in relation to clinicopathological parameters and patients' survival. The majority of samples contained a significant amount of B lymphocytes, predominantly dispersed in the stroma surrounding tumor deposits (mean peritumoral and intratumoral densities: 178.7 ± 156.1 vs. 4.9 ± 6.9 cells/mm², respectively). B cells organized in follicle-like aggregates were also observed in 26% of the samples. B-cell density correlated with that of activated (CD25(+) or OX40(+)) T lymphocytes. Infiltration by CD20(+) lymphocytes did not correlate with tumor thickness, while the presence of B-cell aggregates was observed more frequently in thick melanomas. On the other hand, B-cell infiltration was more pronounced in nonmetastatic or lymph node metastatic tumors, compared to visceral metastatic ones. Accordingly, high number of these cells provided significant survival advantage (P = 0.0391 and P = 0.0136 for intra- and peritumoral infiltration, respectively). Furthermore, combination of peritumoral B-cell density with the number of activated T lymphocytes identified patient subgroups with different disease outcome, which was most favorable in the case of high density, while very poor in the case of low density of both cell types. Multivariate survival analysis identified tumor thickness and CD20(+)/OX40(+) cell density combination as significant independent prognostic factors. Taken together, our results show correlation between low number of CD20(+) B lymphocytes and melanoma progression, indicating a possible role of tumor-infiltrating B cells in antitumoral immune response. It was also reflected in better outcome of the disease since the density of B lymphocytes alone as well as in combination with that of activated T cells proved of prognostic importance in patients with malignant melanoma.

Regulatory T cells (Tregs) have been implicated as inhibitors of antitumor immune reactions. However, data on the relevance of their prevalence at tumor sites in influencing disease outcome are controversial. The aim of our study was to investigate the role in tumor progression and the prognostic impact of the density of lymphocytes expressing FOXP3, a transcription factor expressed predominantly by CD4(+)CD25(+) Tregs, in primary cutaneous melanoma. We examined the infiltration of FOXP3(+) cells by immunohistochemistry in tumor samples from 97 patients and evaluated in relation to patient and tumor parameters. The degree of infiltration by FOXP3(+) cells did not show correlation with the thickness of melanomas. Moreover, no associations were found with metastasis formation during the 5-year follow-up period, patient survival, or any other clinicopathologic parameters studied. These results suggest that the presence of FOXP3(+) lymphocytes in primary tumors is not of prognostic importance in human cutaneous melanoma.

As the most potent antigen presenting cells, dendritic cells (DCs) play key roles in the immune response against tumors. Their density in the tumor tissue has been associated with prognosis in patients with various cancers. However, few studies have been aimed at the presence and maturation state of DCs in cutaneous melanoma, with regard to their potential clinical correlates. In this study, the density of DCs expressing CD1a and the maturation marker DC-LAMP was determined by immunohistochemistry in primary tumor samples from 82 patients with cutaneous malignant melanoma. Intratumoral and peritumoral cell densities were analyzed in relation to tumor thickness and the subsequent development of metastases, as well as to patients' survival. CD1a(+) DCs were found both infiltrating melanoma cell nests and in the surrounding stroma, while DC-LAMP(+) mature DCs were generally confined to the peritumoral areas, associated with lymphocytic infiltrates. DC density values significantly correlated with the number of activated (CD25(+) or OX40(+)) T lymphocytes (p < 0.001). The degree of infiltration by CD1a(+) and DC-LAMP(+) DCs showed strong inverse correlation with the thickness of melanomas (p < 0.001). High peritumoral density of mature DCs was associated with significantly longer survival (p = 0.0195), while density of CD1a(+) cells had a prognostic impact of borderline significance (p = 0.0610). Moreover, combination of high peritumoral CD1a(+) or DC-LAMP(+) cell density with high number of CD25(+) or OX40(+) lymphocytes identified patient subgroups with more favorable survival compared to other subgroups. A multivariate survival analysis involving DC and activated T-cell densities alone and in combinations, as well as traditional prognostic factors, identified high DC-LAMP(+) cell/high OX40(+) cell density and Breslow index as independent predictors of good prognosis. These results suggest that the presence of CD1a(+) DCs primarily depends on the thickness of melanomas, without direct relationship with the patients' survival. On the other hand, the density of mature DCs, especially in association with that of activated T cells, proved of prognostic importance, suggesting that these parameters could be considered as signs of a functional immune response associated with better outcome of the disease.

Vascularization and host response to malignant tumors may have common molecular regulators, therefore, we analyzed the relationship between microvessel density (MVD) and tumor infiltrating cells in cutaneous malignant melanoma. Density of lymphocyte subpopulations, macrophages, dendritic cells and CD34(+) microvessels was determined by immunohistochemistry in primary tumor samples from fifty-two patients with melanoma thicker than 1 mm. Intratumoral MVD did not show significant association with infiltration for any of these cell types. In the case of peritumoral reactive cell densities analyzed in the whole patient population, a positive correlation of MVD was found with CD3(+) T cell density. This association was stronger in melanomas >4.0 mm and in visceral metastatic tumors. In these subgroups similar phenomenon was observed for CD8(+) cells. We found significant correlation of MVD with CD68(+) macrophage density only in the highest thickness category, and weak associations with B-cell and dendritic cell infiltration in visceral metastatic cases. MVD did not vary significantly in tumors categorized according to thickness, localization, ulceration or histological type. However, both intratumoral MVD and macrophage infiltration were significantly higher in male patients compared to females. The correlation of immune cell density with tumor vascularization and gender differences in vascularity and macrophage infiltration of melanoma deserve further attention.

As previous studies suggested the expression of a 12-LOX enzyme in murine and human melanoma cell lines, the primary aim of this project was to genetically identify the 12-LOX enzyme (platelet-, leukocyte- or epithelial form). By using reverse transcriptase-polymerase chain reaction, sequencing and various immunological techniques we have demonstrated conclusively the expression of the platelet-type 12-LOX in human melanoma cells of different origin, in their transplanted xenografts and in fresh human skin tumors. Furthermore, we found that p12-LOX is able to provide a survival signal for melanoma cells since inhibition of the enzyme by general LOX or selective 12-LOX inhibitors induced apoptosis in vitro. p12-LOX of human melanoma has been shown to be involved in the control of the metastatic phenotype, since we have detected the upregulation of the 12-LOX protein expression in spontaneously metastasizing xenografts and in thick human skin tumors (> 3.0 mm) characterized by high risk for the development of metastasis. Co-expression of two megakaryocytic genes, p12-LOX and alphaIIb integrin chains, was found to be a frequent phenomenon in human melanoma (approximately 70%) suggesting a common regulatory defect in this tumor., (Copyright 2004 Lippincott Williams & Wilkins)

Intratumoral vessels are different both structurally and phenotypically, and this may have clinical significance. In this study we analysed the expression of an adhesion molecule--vascular adhesion protein-1 (VAP-1)--in melanoma-associated blood vessels in 28 primary skin melanoma cases using immunocytochemistry and immunoelectron microscopy. We have found that VAP-1 protein expression is significantly decreased in intratumoral vessels compared with peritumoral ones; this difference was independent of the tumour thickness. Loss of VAP-1 protein expression occurred in both endothelial and smooth muscle cell components. Unlike in other cancer types, the VAP-1 protein expression of intratumoral vessels did not correlate with the density of cytotoxic T-lymphocytes or dendritic cells. On the other hand, the 5-year survival of melanoma patients with low VAP-1 protein expression in intratumoral blood vessels (< or =25%) was lower (26.3%) than in patients whose VAP-1 expression was higher (42.6%, P=0.0632). These results support the idea that the phenotype of intratumoral blood vessels is important in the progression of malignant melanoma.

The central role of T cells in antitumor immunity is well established. However, tumor progression, often seen in the presence of substantial lymphocytic infiltration, suggests that these T cells are not capable of mounting an effective immune response to control tumor growth. Evidence has accumulated that T lymphocytes infiltrating human neoplasms are functionally defective, incompletely activated, or anergic. Therefore, when characterizing the immune competent cells within lymphoid infiltrates of tumors, it is important to assess their activation state. We investigated the expression of two T-cell activation markers, interleukin 2 receptor alpha (CD25) and OX40 (CD134), by immunohistochemistry in primary cutaneous melanoma samples of 76 patients and analyzed it in relation to tumor stage and tumor progression (>5 years follow-up), as well as to patients' survival. We found that the degree of infiltration by CD25(+) and intratumoral OX40(+) lymphocytes showed a tendency to decrease in thicker melanomas. The frequency of samples with high numbers of peritumoral CD25(+) and OX40(+) cells was significantly lower (P = 0.0009 and P = 0.0087, respectively) in melanomas developing distant visceral metastases, compared with nonmetastatic or lymph node metastatic tumors. For both activation markers studied, high peritumoral densities were associated with longer survival by univariate analysis (P = 0.0028 and P = 0.0255 for CD25 and OX40, respectively), whereas peritumoral OX40(+) lymphocyte infiltration had an impact on survival also in multivariate analysis (P = 0.035). The results suggest that the presence of lymphocytes expressing the T-cell activation markers CD25 or OX40 shows correlation with tumor progression as well as with patients' survival in cutaneous malignant melanoma.

Approximately one third of clinical Stage I melanoma patients will experience disease recurrence. The author reviews the main prognostic factors predicting the outcome of melanoma patients, the incidence, pattern and time of first metastases. Of all recurrences, two third will occur earlier by the lymphatic, and one third later by the hematogenous pathway. 75-80% of recurrences develop in the first 3 years, 3-4% of metastases occur after 10 years of disease-free interval. The data emphasize the value of lifelong follow-up.

The role of alphaIIbbeta3 integrin in regulating platelet function is well appreciated, whereas its role in tumor progression and metastasis is not. The purpose of our study was to determine a functional relevance to expression of alphaIIbbeta3 integrin in cells derived from human solid tumors. A study of human melanoma biopsies (n = 24) showed that alphaIIbbeta3 expression increased with tumor thickness, which is indicative of metastatic propensity. Expression of alphaIIbbeta3 was 8% (+/-1.8), 33% (+/-10.4) and 62% (+/-5) in melanomas ranging in thickness from 0-1.5 mm, 1.5-4.0 mm and >4 mm, respectively; alphavbeta3 was equally high all categories. To determine biological function, we stably transfected alphaIIbbeta3 into human melanoma cells that express alphavbeta3, but not alphaIIbbeta3. Surface expression of alphavbeta3 remained unaltered between alphaIIbbeta3 (+) and mock transfected counterparts. The alphaIIbbeta3 (+) cells possessed increased ability to adhere, spread and migrate on fibrinogen. They had decreased ability to attach, spread and migrate on vitronectin. Immunocytochemistry showed that expression of alphaIIbbeta3 displaced alphavbeta3 from focal contact points. When implanted subcutaneously into SCID mice, the alphaIIbbeta3 (+) cells developed approximately 4-fold larger tumors when compared to their mock counterparts and the level of apoptosis was reduced within the tumors. Results suggest that co-expression of the 2 beta3 integrins, alphavbeta3 and alphaIIbbeta3, in human melanoma cells enhanced cell survival and promoted growth in vivo., (Copyright 2002 Wiley-Liss, Inc.)

This study was undertaken to determine the role and the fate of the peritumoural vascular plexus during the vascularization of human malignant melanoma (hMM) and in an appropriate murine melanoma model system. The prognostic significance of the vascularity of different tumour areas was also evaluated. Despite morphometry revealing several-fold higher microvessel densities (MVDs) in the peritumoural tissue than at the centre of the tumour, the development of visceral metastases of hMM was exclusively correlated with the MVD of the tumour centre. Furthermore, the 5-year survival of the patient group with low tumour centre MVD (<30/mm(2), n=29) was 100%, compared to 1/16 patients alive with high tumour centre MVD (>30/mm(2), n=16). Morphometric analysis and three-dimensional reconstruction of vessel networks of both human and murine melanomas showed clearly that the peritumoural vascular plexus present at the melanoma base is continuously being incorporated into the growing tumour mass. Once vessels become incorporated, sprouting ceases and the proliferating endothelial cells (EC) take part only in vessel dilatation. Moreover, the immunohistochemical and ultrastructural characterization of microvessels demonstrated that the pericyte coverage of endothelial tubes was complete in all of the investigated areas, in both human and murine melanomas., (Copyright 2002 John Wiley & Sons, Ltd.)

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.

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.

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.

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.

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 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.

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.