The fragile X mental retardation protein (FMRP) is lacking or mutated in patients with the fragile X syndrome (FXS), the most frequent form of inherited intellectual disability. FMRP affects metastasis formation in a mouse model for breast cancer. Here we show that FMRP is overexpressed in human melanoma with high Breslow thickness and high Clark level. Furthermore, meta-analysis of the TCGA melanoma data revealed that high levels of FMRP expression correlate significantly with metastatic tumor tissues, risk of relapsing and disease-free survival. Reduction of FMRP in metastatic melanoma cell lines impinges on cell migration, invasion and adhesion. Next-generation sequencing in human melanoma cells revealed that FMRP regulates a large number of mRNAs involved in relevant processes of melanoma progression. Our findings suggest an association between FMRP levels and the invasive phenotype in melanoma and might open new avenues towards the discovery of novel therapeutic targets.

Background: Erythroderma can be caused by inflammatory dermatoses or cutaneous T-cell lymphoma. Even if chemokines and their receptors are involved in the skin-selective lymphocyte recruitment, their role in inflammatory erythroderma is yet unclear. Objective: To evaluate the chemokine release (TARC, MDC, IP-10) and to define the expression pattern of Th1- (CCR5, CXCR3) and Th2-related (CCR4) chemokine receptors in inflammatory erythroderma and Sézary syndrome (SS). Materials and Methods: Flow cytometry has been carried out on both circulating and skin-infiltrating T lymphocytes; serum chemokine levels have been evaluated using ELISA techniques. Results: CCR4, CCR5 and CXCR3 were expressed on about 40% of peripheral blood lymphocytes and on the majority of skin-infiltrating lymphocytes in the inflammatory erythroderma patients, whereas the leukemic CD4+CD26– subpopulation in SS was characterized by a high CCR4 expression without a concurrent increase in CCR5 or CXCR3. TARC, MDC and IP-10 serum levels were significantly increased in both erythrodermic and SS patients. Conclusions: Our results confirm that SS is a Th2 disorder with a selective expression of CCR4, whereas inflammatory erythroderma shares an overexpression of both Th1- and Th2-related chemokine receptors, suggesting an activation of different pathways driving reactive lymphocytes to the skin.

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Background: The new AJCC classification has highlighted some particular risk factors for squamous cell carcinoma (SCC) relevant for prognosis. Incomplete excision is not infrequent in SCC. The aim of this study is to examine features that can predict an incomplete excision on the basis of the new AJCC classification and to review the literature on this topic. Materials and Methods: 81 SCC patients were included. All patients were submitted to excisional biopsy with a margin of at least 4 mm from the clinical edges as recommended. Histological characteristics of the lesions analysed were maximum diameter, grading, site, Breslow thickness, Clark level, deep tissue invasion (neural, bone, muscle), presence of ulceration and positivity of the margins. Results: The average Breslow thickness was 3.93 mm. Out of the 81 patients included, 14 showed involved margins. The 2 parameters that were implicated in predicting involvement of the margins in the multivariable model were Breslow thickness and location of the lesion on the ear or lip. Grading was not associated with involvement of margins. Conclusion: According to the new AJCC classification, this study could be useful to plan the most suitable surgical technique in order to avoid the risk of incomplete surgery.

Objectives: This study was aimed at investigating the prognostic role of multiple lymph node basin drainage (MLBD) in patients with positive sentinel lymph node (SLN) biopsy. Background: MLBD is frequently observed in patients with trunk melanoma undergoing SLN. The prognostic value of MLBD in SLN-positive patients is still debated. Methods: Retrospective data from 312 trunk melanoma patients with positive SLN biopsy (1991-2012) at 6 Italian referral centres were gathered in a multicentre database. MLBD was defined at preoperative lymphoscintigraphy. Clinical and pathological data were analysed for their association with disease-free interval (DFI) and disease-specific (DSS) survival. Results: MLBD was identified in 34.6% of patients (108/312) and was significantly associated with >1 positive SLN (37 vs. 15.2%; p < 0.001) and with >1 positive lymph node (LN) after complete lymph node dissection (CLND) (50.9 vs. 34.8%; p = 0.033). No differences were observed according to drainage pattern in patients who had negative and positive non-SLN at CLND. MLBD was not associated with either DFI or DSS. Multivariate analyses showed that tumour thickness, ulceration, and number of metastatic LNs were associated with worse DFI and DSS, while regression confirmed its protective role in survival. Conclusion: In positive SLN patients, MLBD has no association with survival, which is mainly related to American Joint Committee on Cancer (AJCC) prognostic factors. Since the overall number of positive LNs drives the prognosis, the importance of a CLND in all the positive basins is confirmed.