According to the high marker level in lung and liver metastases, the marker might be useful in monitoring both patients with disease free ocular melanomas, to detect liver metastasis and high-risk patients after surgical removal of the primary tumour to reveal lung metastases.
Serum S-100 protein is widely used as a marker of melanoma and since 5-S-cysteinyldopa (5-S-CD) is a precursor of melanin its serum and urinary levels can reflect melanoma progression. In this study we examined the concentration changes of serum S-100 protein and 5-S-CD in 252 melanoma patients of different clinical stages. Serum samples were taken from 252 melanoma patients at 860 times, from June 1996 to July 1998. The serum S-100 protein was measured by the immunoluminometric assay, levels of 5-S-CD was determined by HPLC. The value of S-100 protein in patients with primary melanoma (0.11m mg/l) and in patients without symptoms (0.15 m mg/l) ranged around the normal level (0.01 0.12 m mg/l). There was a significant difference between the values of patients with or without symptoms. There was a similarly significant difference between the S-100 values of clinical Stage I (0.11 mg/l) and Stage III (2.91 mg/l) as well as between those of clinical Stage II (0.47 mg/l) and Stage III (2.91 mg/l), respectively. Analyzing the values of patients with symptoms we observed significant difference between the S-100 protein values of patients with primary tumor and those with solitary or multiple distant metastases. In case of 5-S-CD significant difference was found between clinical Stage I and III as well as clinical Stage II and III. Furthermore, there was a significant difference between the mean marker values of patients with primary tumor, lymph node, lung metastasis and clinical stage III.
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.
Objective: Serum S-100B is a reliable tumor marker of malignant melanoma, but efficient use is restricted to patients with metastatic disease. Therefore, the aim of our study was to assess serum S-100B levels at different stages of malignant melanoma and to compare these levels with the expression of the S-100B phenotype in primary tumors and lymph node metastases. Methods: Fifty-nine patients were included in this study; serum S-100B protein was measured using an immunoluminometric assay while the expression pattern in the primary tumor was determined by immunohistochemistry using an anti-S-100B monoclonal antibody. Results: Serum S-100B concentrations were significantly elevated in stage III (p = 0.01) patients, with normal levels in stage I–II. The most frequent S-100B protein expression pattern of the melanoma tissue was found to be diffuse staining observed in around half of the cases (52.5%) followed by heterogeneous (30.5%) and focal patterns (17%), being independent of the stage as well as the lymph node involvement. In stage I–II patients, the various staining patterns did not correlate with the serum concentration of the S-100B protein, while in stage III patients with heterogenous or diffuse S-100B staining patterns in tumor tissue, the serum marker concentration was significantly higher (p < 0.05) than in patients with focal staining. Furthermore, S-100B staining of the melanoma tissue also differed (low/negative, medium and strong staining), and serum marker concentrations corresponded to the pattern of the staining intensity. In stage I–II, only strong staining was associated with elevated serum S-100B concentrations while in stage III medium and strong staining was found to be associated with significantly higher serum marker concentrations compared to patients with tumors with low/negative staining (p < 0.05). Conclusions: In malignant melanoma characterized by focal and/or low S-100B staining in the tumor tissue determined by immunohistochemistry, S-100B monitoring in the serum may not suffice to detect disease progression.
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