Serum tryptase levels in melanoma patients: case-control study and review of the literature.

BACKGROUND: Serum tryptase results from the constant release of the enzyme from mast cells and serum tryptase levels are commonly considered to be related to the total number of mast cells. They are increased in several malignancies, as pancreatic carcinoma, angiosarcoma, hepatic carcinoma and proliferative and/or non-proliferative hematological disorders. Contrariwise, it has been reported that the number of tryptase- and chymase-positive mast cells was lower in deeply invasive melanoma compared to in-situ melanoma and dysplastic nevi. Considering the underlying pathophysiological linkages between mast cells and melanocytes and that serum tryptase is related to angiogenesis, tissue-degrading proprieties and metastatization, we have decided to evaluate serum tryptase levels in melanoma patients and in a healthy control. METHODS: We performed a case-control study evaluating serum tryptase in melanoma and in healthy group. Starting from an initial general analysis, we have performed a sub-analysis for each sample. RESULTS: In general population serum tryptase was statistically higher in elderly patients. Generally, in melanoma patients, median serum tryptase was in lower normal range. We found a decreasing of serum tryptase levels from the healthy control to thin (≤1.00 mm Breslow thickness), reaching the lowest levels in thicker melanoma (≥1.01 mm Breslow thickness), in ulcerated and metastatic melanoma. CONCLUSIONS: Tryptase may have a protective role in melanoma or in the early stage of the tumorigenesis. Serum tryptase is an easy and useful biomarker to better investigate melanoma biology.

SERUM PROLACTIN IN MELANOMA PATIENTS WITH INTERFERON ALPHA2B TREATMENT.

UNLABELLED: The authors' interest was focused on prolactin status in patients with melanocytic lesions and on changes induced by interferon treatment in melanoma patients. MATERIAL AND METHOD: The study lasted 5 years and included 128 melanoma patients, 48 dysplastic nevi patients and 48 healthy volunteers. Sixty melanoma cases were selected after surgical removal of tumor and divided into 2 groups: 30 patients with 10 MUmp(-1) interferon alpha2b treatment, three times a week, one year and 30 patients without interferon treatment. Prolactin assessment was made at inclusion in the study, after surgical removal of tumor, when patients started the treatment, after 1, 6, 12 months of treatment and 6 months after treatment end. RESULTS: In melanoma patients, high values of prolactin (10.55 ± 5.94 ng/ml) were detected when compared with dysplastic nevi group (5.94 ± 2.87 ng/ml) and control group (5.74 ± 3.66 ng.ml). Prolactin levels decreased after surgical removal of melanoma, significantly increased during interferon treatment and returned to baseline few months after the immunomodulatory treatment. CONCLUSIONS: The treatment with interferon alpha2b stimulated reversible and non-cumulative prolactin production. Evaluating prolactin in melanoma patients could become necessary in the future, both for finding a possible pituitary disorder, but also for a new pharmacological intervention.

TSLC1 expression discriminates cutaneous melanomas from dysplastic nevi.

Cutaneous melanoma is a malignant tumor of melanocytes that causes the majority of skin cancer-related deaths. However, sometimes, discrimination between dysplastic nevi and early melanomas is difficult, even for experienced pathologists. Besides histology, the silencing of tumor suppressor genes aids in the diagnosis of melanoma. We have shown previously that tumor suppressor in lung cancer 1 (TSLC1) is a tumor suppressor gene, and its silencing through aberrant promoter methylation is associated with the generation of cutaneous melanoma. To examine TSLC1 expression in melanocytic skin lesions to determine whether it can serve as a diagnostic marker in histologically questionable lesions. Cytoplasmic localization of the expression of the TSLC1 gene was detected by immunohistochemistry; the levels of TSLC1 mRNA and protein were detected by quantitative real-time reverse transcription-PCR and western blot, respectively. Using immunohistochemistry, the average TSLC1 expression levels in cutaneous melanomas decreased approximately 3.6-fold (n=20) as compared with dysplastic nevi (n=30) and 3.7-fold as compared with normal skin (n=25). The average expression levels of TSLC1 mRNA and protein in dysplastic nevi lesions and normal skin were significantly higher than the levels in cutaneous melanomas. No significant changes in TSLC1 mRNA and protein expressions were found between normal skin and dysplastic nevi. Our results show that a loss of TSLC1 frequently occurs in cutaneous melanoma, and indicate that it could serve as a diagnostic marker for cutaneous melanoma in histologically questionable lesions.

Biological value of melanoma inhibitory activity serum concentration in patients with primary skin melanoma.

Melanoma inhibitory activity (MIA) protein was identified in significant quantities in primary and metastatic malignant melanomas, where it has an important role in promoting tumor development and progression. Our hypothesis was that MIA serum level will be elevated in patients with metastases or local spreading of the disease before any symptom of such progression is clinically apparent. We compared MIA serum levels in two groups of patients with primary melanoma; those with positive as opposed to those with negative sentinel lymph nodes. In addition, MIA serum levels were studied in two control groups; patients with dysplastic nevi and patients with basal cell carcinoma. A blood sample was obtained from each patient included in the study and MIA levels were assessed using standard enzyme-linked immunosorbent assay method. Patients with histologically positive sentinel lymph nodes, meaning that tumor cells were found in the lymph nodes, had much higher mean MIA values than any other patient group considered in this study. With mean value of 14.53 ng/ml, it was almost twice as high as mean MIA value in patients with histologically negative sentinel lymph nodes (7.32 ng/ml) and more than twice as high than any of the two control groups (P<0.001). However, neither the classification by Clarke nor the classification by Breslow could be used to distinguish patients with positive sentinel lymph nodes from those with negative sentinel lymph nodes. In our opinion, MIA serum level is the ideal test for screening the tumor spread to sentinel lymph nodes.

Radiation-induced chromatid breaks and DNA repair in blood lymphocytes of patients with dysplastic nevi and/or cutaneous melanoma.

Each chromatid contains a single continuous molecule of double-stranded DNA, so chromatid breaks represent unrepaired DNA double-strand breaks. Frequencies of chromatid breaks after G2 phase x-irradiation were determined in phytohemagglutinin-stimulated blood lymphocytes from normal subjects and from four categories of patients with dysplastic nevi with or without cutaneous melanoma or with melanoma alone. Some cells were treated with an inhibitor of DNA repair replication to determine enzymatic incision activity at damaged sites after exposure to x-rays, UVC, or fluorescent light. Whereas one of 16 normal controls had deficient DNA repair, all 17 patients from families with hereditary dysplastic nevi with or without melanoma (category I) had a deficiency in repair of radiation-induced DNA damage, manifested as an abnormally high frequency of chromatid breaks after x-irradiation or a reduced capacity to incise the damaged sites after UV exposure. Four of 11 patients with sporadic dysplastic nevi alone (category II) and eight of 12 with sporadic dysplastic nevi and melanoma (category III) showed deficient DNA repair after x-irradiation. One of two patients with sporadic melanoma and no dysplastic nevi (category IV) was also deficient in repair of x-ray-induced damage. Deficient DNA repair thus appears to be associated with hereditary dysplastic nevi with or without melanoma. It also characterizes some patients with sporadic dysplastic nevi or melanoma.

Plasma 5-S-cysteinyldopa differentiates patients with primary and metastatic melanoma from patients with dysplastic nevus syndrome and normal subjects.

To determine whether plasma 5-S-cysteinyldopa levels are useful in following up patients at risk for melanoma, we measured plasma 5-S-cysteinyldopa in patients with dysplastic nevus syndrome and/or malignant melanoma and in control subjects. In patients with dysplastic nevus syndrome, plasma 5-S-cysteinyldopa levels did not differ from those in control subjects. Conversely, patients with malignant melanomas had significantly higher plasma 5-S-cysteinyldopa levels than did controls. Those with localized cutaneous malignant melanoma and no distant metastases (Stage I and II disease) had 5-S-cysteinyldopa levels twofold greater than those of control subjects, whereas the levels of those with regional lymph node involvement (Stage III disease) were fourfold greater than those of control subjects. Levels of those with extraregional metastases (Stage IV disease) were 7- to 450-fold higher than those of control subjects. Moreover, plasma 5-S-cysteinyldopa levels correlated with the spread of disease and were useful in distinguishing primary melanoma and Stages III and IV melanoma. We conclude that plasma 5-S-cysteinyldopa may be an important tool for identifying melanoma at an earlier, more curable stage and for following up patients at risk for the development of melanoma, for example, those with dysplastic nervus syndrome.