Prognostic impact of B-cell density in cutaneous melanoma.

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.

FOXP3+ cell density in primary tumor has no prognostic impact in patients with cutaneous 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.

Large randomized study of thymosin alpha 1, interferon alfa, or both in combination with dacarbazine in patients with metastatic melanoma.

PURPOSE: Thymosin alpha 1 (Talpha1) is an immunomodulatory polypeptide that enhances effector T-cell responses. In this large randomized study, we evaluated the efficacy and safety of combining Talpha1 with dacarbazine (DTIC) and interferon alfa (IFN-alpha) in patients with metastatic melanoma. PATIENTS AND METHODS: Four hundred eighty-eight patients were randomly assigned to five treatment groups: DTIC+IFN-alpha+Talpha1 (1.6 mg); DTIC+IFN-alpha+Talpha1 (3.2 mg); DTIC+IFN-alpha+Talpha1 (6.4 mg); DTIC+Talpha1 (3.2 mg); DTIC+IFN-alpha (control group). The primary end point was best overall response at study end (12 months). Secondary end points included duration of response, overall survival (OS), and progression-free survival (PFS). Patients were observed for up to 24 months. RESULTS: Ten and 12 tumor responses were observed in the DTIC+IFN-alpha+Talpha1 (3.2 mg) and DTIC+Talpha1 (3.2 mg) groups, respectively, versus four in the control group, which was sufficient to reject the null hypothesis that P(0) < or = .05 (expected response rate of standard therapy) in these two arms. Duration of response ranged from 1.9 to 23.2 months in patients given Talpha1 and from 4.4 to 8.4 months in the control group. Median OS was 9.4 months in patients given Talpha1 versus 6.6 months in the control group (hazard ratio = 0.80; 9% CI, 0.63 to 1.02; P = .08). An increase in PFS was observed in patients given Talpha1 versus the control group (hazard ratio = 0.80; 95% CI, 0.63 to 1.01; P = .06). Addition of Talpha1 to DTIC and IFN-alpha did not lead to any additional toxicity. CONCLUSION: These results suggest Talpha1 has activity in patients with metastatic melanoma and provide rationale for further clinical evaluation of this agent.

Association of microvessel density with infiltrating cells in human cutaneous malignant melanoma.

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.

Density of DC-LAMP(+) mature dendritic cells in combination with activated T lymphocytes infiltrating primary cutaneous melanoma is a strong independent prognostic factor.

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.

[Malignant tumors of the skin]. / A bor rosszindulatú daganatai.

Skin cancer is a serious public health problem. A significant number of people die from melanoma. The nonmelanoma skin cancers are rarely fatal and rarely metastasizes. The most frequent human tumor, the basal cell carcinoma invade slowly progressively destroying all local tissues. Squamous cell carcinoma is less common than its basal cell equivalent but it usually has a more aggressive biological behaviour. It is imperative that the primary care physicians are aware of the scope of the problem. Skin cancer is common and fortunately visible. The recognition and appropriate management of skin cancer is the subject of this article

Relationship between sentinel lymph node status and regression of primary malignant melanoma.

The prognostic significance of spontaneous regression of primary melanoma is a controversial issue. Studies on sentinel lymph node status and circulating tumour cells may represent a step towards a better understanding. The clinical details of 269 melanoma patients who underwent sentinel lymph node biopsy were analysed. Correlation was sought between the parameters of the primary tumour, particularly tumours showing a partial intermediate level of regression, and sentinel lymph node status. The presence of circulating tumour cells was studied by reverse transcription-polymerase chain reaction for tyrosinase messenger RNA preoperatively in 94 patients. Of the examined tumours, 27.8% showed histological features of a partial intermediate level of regression. Regressive tumours were localized predominantly on the trunk (P=0.006), were significantly thinner (P<0.0000) and were less frequently ulcerated (P=0.003) than tumours without regression. Moreover, the majority of regressive melanomas were of the superficial spreading type (P<0.0000) and their sentinel node status was more favourable (P=0.026). We demonstrated the presence of circulating tumour cells in five of 26 (19.2%) regressive and 19 of 68 (29.4%) non-regressive tumours. The difference was not significant (P=0.32). By multivariate analysis, however, the Breslow thickness and ulceration of the primary tumour were predictors of the sentinel lymph node status, in agreement with literature data. A partial intermediate level of regression of the primary tumour did not affect unfavourably the sentinel lymph node status in our study. We failed to demonstrate a significant relationship between the presence of circulating tumour cells and either primary tumour regression or the sentinel lymph node status.

[Etiologic factors of malignant melanoma in young adults]. / Fiatalkori melanomák etiológiai tényezoi.

BACKGROUND: Malignant melanoma is the most aggressive type of skin cancers, involving the cutis and the mucosa. Its incidence keeps increasing dramatically in the last decades. It appears rarely in childhood. The main environmental risk factors are: excessive sun exposure and severe sunburns in both childhood and adolescence. Skin phototype, number of nevi, presence of congenital nevi (especially giant congenital nevi) and non-melanoma skin cancer in previous history refer to increased risk. Investigations of genetical factors have come to the front. The role of hormonal influences and traumas are recurring questions. AIM: The presence of melanoma typically concerns the middle-aged population. The purpose of this study was to determine the main risk factors, etiology factors and predisposing pediatric conditions in development of melanoma in young adulthood (under the age of 30). METHOD: A total of 70 new, histologically verified melanoma patient under 30 years were examined between 1993-2003 with a retrospective study. Results of questionnaire based survey and clinical data base about melanoma risk factors were also analysed. RESULTS: 5% of patients had giant congenital nevi, although in half of the patients (19/40) more than 20 moles were found. On the basis of patients' histories 57.5% of melanomas developed on a nevus existing from birth or childhood. 30% of melanomas developed on a pigmented brown alteration which rose on the normal skin. About 1/3 of patients had fair skin type and almost all patients (38/40) suffered from erythematous sunburn at first sunbath. Melanoma developed mostly on the trunk and lower extremities. 51.5% of patients belonged to Stage I (Breslow thickness below 1 mm in 33%). CONCLUSION: There were 70 young (under 30 years) patients were treated for malignant melanoma at the Dermatology Department of the National Institute of Oncology in Budapest from 1993 till 2003. The incidence of melanoma under the age of 30 was 3.3%. In young adulthood the main risk factors were the number of atypical nevi and repeated or severe sunburns in childhood. The skin type was also an important risk factor. 50% of the melanomas in young women developed on the trunk. Authors could not prove any relationship among hormonal factors, pregnancy and the development of the melanoma.

[Primary anorectal melanoma--an uncommon disease with a poor prognosis]. / Primer anorektális melanoma--egy ritka, de igen rossz prognózisú betegség.

Primary anorectal melanoma is a rare disease with poor prognosis. The optimal treatment of this disease is not well defined. The majority of patients develop generalised recurrent disease and die despite radical surgical treatment. Screening for colorectal cancer may help to detect this disease earlier and the early diagnosis should give better outcome. We present a case report and evaluate--based on literature--epidemiology, most common symptoms, histopathology, diagnosis, treatments and the prognosis of primary anorectal melanomas.

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. METHODS: Fluorescence in situ hybridisation was performed using c-myc and centromeric 8 (C8) probes on 68 lesions (28 nodular melanomas [NMs], 26 superficial spreading melanomas [SSMs], and 14 metastases). To assess the ploidy pattern, copy number distribution of seven different chromosomes was also investigated. RESULTS: All tumours showed aneuploid populations for at least three chromosomes. Whereas 61% of the NMs exhibited extra c-myc copies, only 27% of SSMs showed increased gene dosage. The c-myc/C8 ratio exceeding 1.5 was significantly higher in NMs (P = 0.01). High level amplification was seen only in NMs. An elevated c-myc/C8 ratio was higher than 1.5 in only four metastases. CONCLUSION: Our data show that c-myc copy number alterations differ in the two melanoma subtypes and are associated with the advanced stage of the disease. The less frequent amplification of the c-myc gene in metastatic lesions indicates that it may play an important role in the development of an invasive potential rather than in the metastatic process.

[Role of S100B protein in neoplasms and other diseases]. / Az S100B protein marker szerepe daganatokban és más kórképekben.

The S100 protein family constitutes the largest subgroup of the Ca binding proteins. To date 20 members of the family were discovered. S100 proteins regulate intracellular processes such as cell growth and motility, cell cycle regulation, transcription and differentiation. S100B protein is expressed constitutively by brain astrocytes. Serum S100B protein concentration in Stage II-III-IV melanoma is a reliable prognostic marker. The serum level of S100B protein is significant independent prognostic marker in respect to disease specific survival, it is a relevant marker for therapy monitoring and patient follow-up. It is recommended to determine the S100B expression pattern and intensity of the primary tumour of melanoma before therapy monitoring. Elevated S100B levels were published after head trauma, subarachnoidal haemorrhage and stroke. Furthermore, it indicates blood-brain barrier dysfunction. S100B protein was used to determine the cerebral damage after cardiovascular surgery as well.

T-cell activation marker expression on tumor-infiltrating lymphocytes as prognostic factor in cutaneous 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.

Clinical significance of sentinel lymph node involvement in malignant melanoma.

In the period 1997-2002, sentinel lymph node (SLN) surgery was performed on 179 primary skin melanoma patients, one to two months after the removal of the primary. Staining with patent blue was combined with an isotope technique. Histological evaluation of the sentinel lymph nodes was performed in serial sections. Immunohistochemical detection of S100, HMB-45, or Melan-A was used in the case of suspected micrometastases. Demonstration of positive sentinel lymph node was followed, preferably within 2-3 weeks, by regional block dissection. In these cases interferon-a2 in low doses or BCG immune therapy were applied as adjuvant therapy. Bimonthly follow-up of the patients included physical examination and the use of imaging techniques as specified in the melanoma protocol. Sentinel lymph node surgery was successful in 177/179 cases (98%). Positive sentinel lymph node was identified in 26/177 patients (14.7%). In node positive patients the thickness of the primary tumour was significantly greater than that of node negative ones (p<0.00001). Patients with micrometastases had significantly poorer symptom-free and overall survival by the Mantel-Cox test than those of the other group (p=0.0001 and p=0.0007 respectively). Comparison of the tumor thickness and positive SLN by discriminance analysis, yielded 81.7% and 79.9%, respectively for correct classification rates. Based on our study and data from the literature, we suggest SLN-positivity as equally strong poor prognosis factor for skin melanoma as the tumor thickness.

Malignant mucosal melanoma of the head and neck.

Mucosal melanomas comprise about 1% of all malignant melanomas and exhibit far more aggressive behaviour than that of skin melanomas: they are more inclined to metastatize into regional and distant sites or recur locally, regionally or in distant locations, resulting in a high rate of cause-specific death. Mucosal melanomas in the head and neck region account for half of all mucosal melanomas, occurring mainly in the upper respiratory tract, oral cavity and pharynx. They appear with equal gender distribution and with a peak incidence in the age range 60-80 years. In consequence of their hidden location, they are usually diagnosed in a locoregionally advanced clinical stage, with a rate of 5-48% of regional and 4-14% of distant dissemination. The typical therapeutic approach is surgery, postoperative irradiation and systemic therapy. Local control with either surgery or radiotherapy is frequently (60- 70%) achieved, but the rates of local, regional and distant recurrences are high (50-90%, 20-60% and 30-70%, respectively). The reported 5-year actual survival rates are poor (17-48%), which is attributed mainly to a haematogenous dissemination. These characteristics demonstrate that identification of the precursor lesions and more effective local and systemic approaches are needed to improve the therapeutic results.

[Milestones leading to new perspectives in melanoma therapy]. / Megújuló szemlélethez vezeto mérföldkövek a melanoma történetébol.

The author stresses, out of the abundant literature of melanoma, those new pieces of information that have changed the conventional therapeutic approach to melanoma. Elements of melanoma progression leading to a rational transformation of the dogmatic radical surgery are described. In addition, the phenomenon of regression, still requiring further investigations, is also dealt with, as well as the hormonal dependence of melanoma, which has practical importance in the management of some problems, e.g. indication of pregnancy interruption, hormonal contraception, and hormon substitution therapy in postmenopausa. The limited effectiveness of conventional complex tumour killing mechanisms (chemotherapy and radiotherapy) necessitates new therapeutic strategies based on tumour biological knowledge. Finally, the fields of application of vaccination and antiangiogenic and gene manipulation techniques are touched upon.

[Naevus pigmentosus and melanoma]. / A naevus pigmentosus és a melanoma.

Clinical observations and histological findings support the relationship between pigmented naevi and melanoma. The author describes the morphological characteristics of congenital, acquired and atypical naevi in relation to the appearance of melanoma. On the basis of clinical observations, in harmony with other investigators, the author advises patients to perform self examination and to undergo regular survey of numerous atypical naevi by a dermatologist. In fact, any of the atypical pigmented naevi present in high number may be a precursor lesion. Patients with such lesions are at higher risk of melanoma development.

[Report on clinical observations obtained with sentinel lymph node surgery in malignant melanoma and during their follow-up at the Department of Dermatology, National Institute of Oncology, Budapest]. / Sentinel nyirokcsomó-biopszia melanomában. Klinikai tapasztalatok az Országos Onkológiai Intézetben.

OBJECTIVES: Report on clinical observations obtained with sentinel lymph node surgery for malignant melanoma and during follow-up at the Department of Dermatology, National Institute of Oncology, Budapest. PATIENTS AND METHOD: In the period from November, 1997 to September, 2002, the above surgical intervention was made with 179 patients having primary tumour, one to two months after primary tumour removal. Staining with patent blue was combined with isotope technique. The primary melanoma and the pertaining sentinel lymph node(s) were removed. Histological evaluation of the sentinel lymph nodes was performed in serial sections. Immunohistochemical detection of S100, HMB-45, or Melan-A was used in the case of suspected micrometastases. Demonstration of positive sentinel lymph nodes was followed, preferably within 2-3 weeks, by regional block dissection. Interferon in low doses or BCG immune therapy were applied as adjuvant therapy. Bimonthly follow-up of the patients included physical examination and the use of imaging techniques as specified in the melanoma protocol. RESULTS: Sentinel lymph node surgery was successful in 177/179 cases (98%). Positive sentinel lymph node was identified in 26/177 patients (14%). In node positive patients the thickness of the primary tumour was significantly greater than that of node negative ones (p<0.0000). Patients with micrometastases had significantly poorer symptom-free and overall survival by the Mantel-Cox test than those of the other group (p=0.0001 and p=0.0007, respectively). In the discriminance analysis of our data, the discriminant function established from tumour thickness yielded 81.7% and the positivity of sentinel lymph nodes 79.9% correct classification rates. CONCLUSION: In good harmony with literature data, positive sentinel lymph node(s) were found in the case of thicker tumours. The involvement of sentinel lymph node indicated a significantly poorer prognosis.

[Laboratory markers of melanoma progression]. / A melanoma progressziójának laboratóriumi markerei.

Extracellular tumour markers may have potential role in the follow-up of patients with malignant melanoma, in therapy monitoring and in prediction of prognosis. In our article circulating tumour markers in melanoma (melanoma inhibitory activity, lipid bound sialic acid, neuron specific enolase, TA90 immune complex, S-100B protein, 5-S-cysteinyldopa, tyrosinase, cytokines, metalloproteinases, LDH) were reviewed. Among laboratory melanoma markers the S-100B protein is the most investigated. S-100B protein has high specificity, appropriate sensitivity and proved to be significant prognostic factor independent from stages. High serum values are associated with shorter survival. However, before S-100B monitoring immunohistochemistry for the detection of S-100B is required. In the case of malignant melanomas with low expression serum S-100B monitoring may not be sensitive enough to follow disease progression. Although the serum concentration of 5-S-cysteinyldopa did not prove to be independent prognostic factor in our previous studies comprising the highest patient number in the literature, the marker was suggested for therapy monitoring. The survival analysis indicated that the elevated 5-S-cysteinyldopa level predicts shorter survival. In spite of the calculated low correlation between the two markers, parallel elevation of S-100B protein and 5-S-cysteinyldopa indicated shorter survival. On the basis of the literature LDH is the most appropriate tumour marker in stage IV to predict prognosis, but its sensitivity and specificity could not achieve that of S-100B protein. S-100B and LDH proved to be similarly reliable in respect to the clinical outcome. Determination of serum concentration of MIA and tyrosinase are also reliable markers in malignant melanoma. The other investigated markers are not well known yet or do not provide useful information to the clinicians.

[The role of PET scan in the diagnosis of malignant melanoma]. / A PET jelentósége a melanoma malignum diagnosztikájában.

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. The authors concluded that FDG PET had the highest sensitivity among the imaging methods in detecting distant metastases of MM.

Comparison of prognostic significance of serum 5-S-Cysteinyldopa, LDH and S-100B protein in Stage III-IV malignant melanoma.

5-S-cysteinyldopa is a precursor of pheomelanin. S-100B protein is a low molecular weight, acidic, calcium binding, cytoplasmatic protein. LDH was defined as the most important serum parameter in disseminated melanoma. The aim of the present study was to compare the prognostic values of serum 5-S-Cysteinyldopa, S-100B and LDH concentrations in Stage III-IV melanoma patients. Serum samples were taken from 179 Stage III-IV melanoma patients at diagnosis. Serum 5-S-CD concentrations were determined by HPLC, S-100B protein by immunoluminometric assay while LDH by UV kinetic method. The mean/median concentrations of LDH, S-100B protein and 5-S-CD in Stage III patients ranged around the normal level. In Stage IV, the markers ranked as S100B = 5-S-CD > LDH for sensitivity, S-100B > LDH > 5-S-CD for specificity and LDH = S100B = 5-S-CD for positive predictive value, respectively. Furthermore, mean marker concentrations of patients with progressive disease differed significantly from nonprogresssive cases (when staging categories have been disregarded). Survival analysis indicated, that the initially elevated LDH and S-100B level in Stage IV disease predicts comparably short survival. Results of our study suggest that these serum marker values correlate well with Stages and disease progression. In Stage IV melanoma, the markers had appropriate sensitivity, high specificity as well as important positive predictive value. Among the studied serum markers S-100B protein and LDH proved to be similarly reliable in respect to the clinical outcome.