The role of spectrophotometry in the diagnosis of melanoma.

BACKGROUND: Spectrophotometry (SPT) could represent a promising technique for the diagnosis of cutaneous melanoma (CM) at earlier stages of the disease. Starting from our experience, we further assessed the role of SPT in CM early detection. METHODS: During a health campaign for malignant melanoma at National Cancer Institute of Naples, we identified a subset of 54 lesions to be addressed to surgical excision and histological examination. Before surgery, all patients were investigated by clinical and epiluminescence microscopy (ELM) screenings; selected lesions underwent spectrophotometer analysis. For SPT, we used a video spectrophotometer imaging system (Spectroshade MHT S.p.A., Verona, Italy). RESULTS: Among the 54 patients harbouring cutaneous pigmented lesions, we performed comparison between results from the SPT screening and the histological diagnoses as well as evaluation of both sensitivity and specificity in detecting CM using either SPT or conventional approaches. For all pigmented lesions, agreement between histology and SPT classification was 57.4%. The sensitivity and specificity of SPT in detecting melanoma were 66.6% and 76.2%, respectively. CONCLUSIONS: Although SPT is still considered as a valuable diagnostic tool for CM, its low accuracy, sensitivity, and specificity represent the main hamper for the introduction of such a methodology in clinical practice. Dermoscopy remains the best diagnostic tool for the preoperative diagnosis of pigmented skin lesions.

Human melanoma metastases express functional CXCR4.

PURPOSE: The chemokine receptor CXCR4 was identified as an independent predictor of poor prognosis in primary melanoma. The aim of the study was to investigate the role of CXCR4 in human melanoma metastases. EXPERIMENTAL DESIGN: CXCR4 expression was evaluated in melanoma metastases and in metastatic cell lines through immunohistochemistry, immunoblotting, immunofluorescence, and reverse transcription-PCR. The function of CXCR4 was tested in the presence of the ligand, CXCL12, through induction of extracellular signal-regulated kinase-1 and -2 (Erk-1 and -2) phosphorylation, proliferation, apoptosis, and migration capabilities. RESULTS: CXCR4 expression was detected in 33 out of 63 (52.4%) metastases from cutaneous melanomas. Metastatic melanoma cell lines expressed cell surface CXCR4; PES 43, Alo 40, and COPA cell lines showed the highest levels of CXCR4 (>90% of positive cells); PES 41, Alo 39, PES 47, POAG, and CIMA cell lines showed low to moderate degrees of expression (5-65% of positive cells). Other chemokine receptors, CCR7 and CCR10, were detected on the melanoma cell lines; CXCL12 activated Erk-1 and Erk-2, the whose induction was specifically inhibited by AMD3100 treatment. CXCL12 increased the growth in PES 41, PES 43, and PES 47 cells under suboptimal (1% serum) and serum-free culture conditions; AMD3100 (1 mumol/L) inhibited the spontaneous and CXCL12-induced proliferation. No rescue from apoptosis was shown but PES 41, PES 43, and PES 47 cells migrate toward CXCL12. CONCLUSIONS: These findings indicate that CXCR4 is expressed and active in human melanoma metastases, suggesting that active inhibitors such as AMD3100 may be experienced in human melanoma.

Adjuvant treatment of malignant melanoma: where are we?

To date, no standard adjuvant therapy have increased overall survival in patients with malignant melanoma (MM). The effect of interferon alpha as a single agent or in combination has been widely explored in clinical trials. Critical reading of the major international randomised trials showed that response to interferon (IFN) in terms of improvement of overall survival (OS) may not be strictly correlated with the used dosage and that duration of therapy may impact disease-free survival (DFS) but not OS. Patients' heterogeneity could be an explanation for the discordant data of the international literature. Indeed, majority of these studies started in late 1980s or early 1990s, when accurate staging procedure were not available yet. The adequate surgical treatment should be considered as an independent variable in the analysis of MM adjuvant protocols. Considering the treatment cost, which is the main goal: DFS, OS or quality of life? Answering these questions is difficult, but some considerations must be taken to put order in this field. Putting together data from all different studies, IFN therapy seems to protect MM patients from recurrences during the entire treatment period and a prolonged IFN therapy seems to improve DFS. The only positive result on OS was demonstrated for high-dose IFN (HD-IFN) in a single study (presenting a relatively short follow-up median) and not confirmed in a subsequent study from the same authors. Considering that low-dose interferon (LD-IFN) is tolerated much better than HD-IFN (about 10% versus more than 70% of cases with grade 3-4 toxicity, respectively), a prolonged LD-IFN (more than 2 years) may represent a reasonable opportunity for MM patients, also considering its advantageous cost-effectiveness. Conversely, considering the improvement of OS as the main target of MM adjuvant therapy, the "wait and watch" attitude remains the only approach to be pursued at present. It is a physician's choice.