Aquaporin-1 Protein Expression of the Primary Tumor May Predict Cerebral Progression of Cutaneous Melanoma.

Brain metastasis is a frequent complication of the progression of malignant melanoma. In a previous study aquaporin 1 (AQP1) protein expression was found to be associated with increased mortality and decreased progression free survival in cutaneous melanoma. To explore further the potential of this marker we studied the AQP1 protein expression in 67 metastatic melanoma patients using immunohistochemistry. Primary tumor samples were acquired from patients with brain (BR) (n = 44) and extra-cranial (EC) (n = 23) metastases, while brain metastatic samples were collected during neurosurgical resection (n = 5). Patients with brain metastases had shorter overall survival (p = 0.02) and significantly higher AQP1 expression in the primary tumors (median H-score = 250 vs. 140, p = 0.044) as compared to patients of the EC metastasis group. AQP1 expression was found to be significantly lower in the brain metastases compared to the corresponding primary tumors (median H-score = 35 vs. 300 p = 0.01). However, in brain metastases AQP1 expression was heterogenous, AQP1 protein was more abundant in the melanoma cells far away from the capillaries as compared to tumor cells adjacent to vessels indicating a hypoxia-driven expression of AQP1. We suggest that AQP1 expression could well be a prognostic marker of brain metastatic potential of human cutaneous melanoma.

Serum concentration of 5-S-cysteinyldopa in patients with melanoma.

BACKGROUND: 5-S-cysteinyldopa (5-S-DC) is a precursor of melanin. Its serum and urinary level can reflect melanoma progression. In this study we examined the concentration changes of 5-S-CD in melanomas of different clinical stages and in patients with different symptoms of melanoma, during and after treatment. METHOD: Serum samples were taken from 252 melanoma patients on 765 occasions, from June 1996 to July 1998. Levels of 5-S-CD were determined by HPLC. RESULTS: The value of 5-S-CD in patients with primary melanoma and in patients without symptoms ranged around the normal level. There was a significant difference between the values of patients with or without symptoms. There was also a significant difference between the 5-S-CD values at clinical Stage I and Stage III, as well as at clinical Stage II and Stage III, respectively. Analysing the values of patients with symptoms we found a significant difference between the mean values of primary tumour and stage III, between values in lymph node metastasis and stage III, between values in lung metastasis and stage III. The tumour burden was found to correlate with a rising marker level. In 7% of the symptomatic patients that had a marker level under the upper limit, amelanotic primary tumour was detected. CONCLUSION: 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.

[The role of intraoperative gamma-probe-guided sentinel lymph node biopsy in the treatment of malignant melanoma and breast cancer]. / Az intraoperatív gamma-próba által vezérelt örszem nyirokcsomó-biopszia jelentösége a melanoma malignum és az emlörák kezelésében.

In the treatment of malignant tumors regional lymphadenectomy is used for two purposes. It is used partly for staging the regional lymph nodes which is a significant and independent prognostic factor and determines the need for adjuvant oncologic treatment and partly for achieving locoregional disease control. Removal of tumor-free lymph nodes by regional lymph node clearance is unnecessary according to our current knowledge. Since the sensitivity and specificity of non-invasive clinical examinations are insufficient in predicting the nodal status the histological study of the regional lymph nodes cannot be abandoned. A new and minimally invasive surgical procedure, the mapping and removal of the first tumor draining lymph node, the sentinel node provides the possibility of pathological nodal staging without performing formal lymphadenectomy. Mapping of the sentinel node can be performed by the use of a radioisotope and intraoperative hand-held gamma-probe or a vital blue dye or a combination of these two. This latter method was used by the authors in 73 patients (25 with malignant melanoma and 48 with breast cancer). Sentinel lymph node biopsy was performed successfully in 92% of patients with melanoma and 90% of patients with breast cancer. In three breast cancer patients the sentinel node inaccurately predicted the axillary status as negative, but is was in 93% accurate in predicting the histologic nodal state. According to our preliminary experiences intraoperative gamma-probe guided sentinel lymph node biopsy is considered a feasible procedure in both malignant melanoma and breast cancer. More experiences are needed before introducing this method in the routine clinical practice.

[Determination of serum S-100 protein and 5-S-cysteinyl-DOPA levels in melanoma patients]. / S-100 protein és 5-S-ciszteinil-DOPA vizsgálata melanomás betegekben.

This was the first time that authors detected se-S-100 and 5-SCD values with patients with malignant melanoma in Hungary. They examined the change of serum S-100 and 5-SCD value parallel. Sera were obtained with 184 melanoma patients 326 times. Patients were ranked into groups on the basis of clinical symptoms: free of symptoms and suffering from it (primary tumour, regional lymph node metastasis, soliter or multiplex distant metastasis). On the basis of the initial results the following have been found: S-100 protein and 5-SCD serum levels had no prognostic value in patients with primary melanoma. Patients without symptoms showed values around the normal level. There was significant difference in both markers between patients with or without symptoms. Significant differences were found between clinical stage I and II, as well as in clinical stage II and III. In the case of S-100 protein there was significant difference between the values of patients with soliter and multiplex distant metastasis.

Effect of modification of membrane saccharides on hormonal imprinting in Tetrahymena.

Concanavalin-A (Con-A) competes with insulin for the insulin binding sites of the receptor, an event resulting in overlapping bonds. If the saccharide components of the receptor are subjected to periodate treatment the binding of insulin decreases and so does the imprinting evoked by it. Simultaneously, the binding of Con-A increase immediately after the treatment and 24 hours following the insulin imprinting. This phenomenon indicates that though the two ligands (i.e. insulin and Con-A) overlap on the intact receptor, alterations in the saccharide component influence their binding though not in the same manner and not in the same direction. Periodate treatment, similarly as observed in mammalian lymphocyte cultures, enhanced the division of Tetrahymenas and the peak of Con-A binding occurred parallel to the peak of division after periodate treatment of equal duration. Periodate treatment disturbed not only the binding of Con-A but that of other lectins as well. It has been concluded that hormonal imprinting requires a physiological condition of the membrane and any disturbance of the membrane will lead to a decrease in the efficacy of imprinting.