Alessandro Scoppola

Dermoscopic patterns of cutaneous melanoma metastases

Although the long experience acquired with the widespread use of dermoscopy has allowed the establishment of criteria for the recognition of benign and malignant skin lesions, very few data are available on cutaneous melanoma metastases. As the characteristic clinical aspects are multiform and even histological evaluation may sometimes be difficult, we have studied and characterized the patterns of cutaneous melanoma metastases in dermoscopy. In this paper, we report dermoscopic data on 130 histologically confirmed metastases observed in 32 patients affected by melanoma, with particular emphasis on dermoscopic features. Nine dermoscopic elements (homogeneous, saccular, amelanotic, polymorphic and vascular patterns, colour, perilesional erythema, pigmentary halo, peripheral grey spots) were studied in 130 cutaneous melanoma metastases and compared with those of 350 melanomas, 150 common naevi, 40 blue naevi, 40 haemangiomas and 50 basal cell carcinomas. The saccular and vascular patterns (especially polymorphic atypical vessels and winding vessels), as well as pigmentary halo and peripheral grey spots, seem to be the most significant elements suggestive of cutaneous melanoma metastases. The interest in and importance of the dermoscopic aspects of cutaneous melanoma metastases cannot be neglected if the American Joint Committee has determined that microsatellitosis and micrometastases are fundamental in the new TNM staging classification for cutaneous melanoma.

Predictors of existential and religious well-being among cancer patients

Well-being and mental health are not only direct functions of amount of stress, but also depend on how people appraise and face critical situations. Spiritual well-being seems to be a central component of psychological health in physically healthy individuals and it offers some protection against end-of-life despair in those with chronic diseases. In this study, 250 out and in-patients with a cancer diagnosis were interviewed with standardised instruments to measure two aspects of spirituality, existential and religious well-being, coping strategies, psychological state, and quality of life (QoL). Using multivariate logistic regression models we found that coping strategies characterized by acceptance and positive reinterpretation of the stressor, and the absence of anxiety disorder, independently increased the likelihood of the existential well-being (Odds Ratio, OR, 7.7, and OR, 4.5, respectively), whereas religious well-being was not significantly associated with these variables. Our findings show that existential and religious well-being may be very different. A spirituality-based intervention could be differently utilized by patients with different beliefs, cognitive and behaviour characteristics. Measure of coping strategies and psychological state should be part of routine management of cancer patients.

High Expression of the Mismatch Repair Protein MSH6 Is Associated With Poor Patient Survival in Melanoma

OBJECTIVES The outcome of patients with primary melanoma (PM) cannot be completely explained based on currently adopted clinical-histopathologic criteria. In this study, we evaluated the potential prognostic value of mismatch repair protein expression in PMs. METHODS We examined the immunohistochemical staining of mismatch repair proteins in 18 benign nevi and 101 stage I to III PMs and investigated their association with tumor clinicopathologic variables and melanoma mortality. RESULTS Expression of MSH2, MLH1, and PMS2 was high in benign nevi and reduced in a subset of PMs. Conversely, MSH6 expression was absent or extremely low in benign nevi and increased in a subset of PMs. In the multivariate analysis, including sex, age, Breslow thickness, and ulceration, high MSH6 expression in PMs (ie, immunostaining in >20% of tumor cells) was significantly associated with an increased risk of melanoma mortality (relative risk, 3.76; 95% confidence interval, 1.12-12.70). CONCLUSIONS MSH6 protein expression can be a valuable marker to improve prognosis assessment in PMs.

Placenta growth factor and neuropilin-1 collaborate in promoting melanoma aggressiveness

The placenta growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family, which shares with VEGF-A the tyrosine kinase receptor VEGFR-1 and the co-receptor neuropilin-1 (NRP-1). In melanoma models, PlGF enhances tumour growth and neovessel formation, whereas NRP-1 promotes the metastatic process. Increased secretion of PlGF and expression of NRP-1 have also been involved in intrinsic or acquired resistance to anti‑angiogenic therapies. In this study we investigated whether PlGF and NRP-1 cooperate in promoting melanoma aggressiveness independently of VEGFR-1. For this purpose, the melanoma cell clones M14-N, expressing NRP-1 and lacking VEGFR-1, and M14-C, devoid of both receptors, were used. M14-N cells are characterized by an invasive phenotype and vasculogenic mimicry, whereas M14-C cells possess a negligible invasive capacity. The results indicated that M14-N cells secrete higher levels of PlGF than M14-C cells and that PlGF is involved in the invasion of the extracellular matrix (ECM) and vasculogenic mimicry of M14-N cells. In fact, neutralizing antibodies against PlGF reverted ECM invasion in response to PlGF and markedly reduced the formation of tubule-like structures. Moreover, M14-N cells migrated in response to PlGF and chemotaxis was specifically abrogated by anti-NRP-1 antibodies, demonstrating that PlGF directly activates NRP-1 in the absence of VEGFR-1. We also compared the levels of PlGF in the plasma of patients affected by metastatic melanoma with those of healthy donors and evaluated whether PlGF levels could be affected by a bevacizumab-containing chemotherapy regimen. Melanoma patients showed a 20-fold increase in plasma PlGF and the bevacizumab-containing regimen induced a reduction of VEGF-A and in a further increase of PlGF. In conclusion, our studies suggest that the activation of NRP-1 by PlGF directly contributes to melanoma aggressiveness and represents a potential compensatory pro-angiogenic mechanism that may contribute to the resistance to therapies targeting VEGF-A.

Information Needs of Patients With Melanoma

Evidence continues to suggest that patients with cancer require more information about their disease and its consequences. To evaluate the information needs of patients with advanced melanoma compared to patients with other malignancies, a cross-sectional study was conducted on 221 unselected patients from the oncology department of a dermatologic hospital In Italy. Patients completed the Edmonton Symptom Assessment System and the Need Evaluation Questionnaire, two standardized tools for symptoms and psychosocial needs assessment. Results highlight that patients with advanced melanoma have, in general, a higher need for information compared to patients with other cancers, even if they report fewer symptoms. Future studies on the needs of patients with melanoma may contribute to tailored and more satisfactory patient-centered care. Recommendations for clinical practice include that particular attention should be paid by the oncology team to the need for a strong therapeutic relationship.

Targeting the PTTG1 oncogene impairs proliferation and invasiveness of melanoma cells sensitive or with acquired resistance to the BRAF inhibitor dabrafenib

The pituitary tumor transforming gene 1 (PTTG1) is implicated in tumor growth, metastasis and drug resistance. Here, we investigated the involvement of PTTG1 in melanoma cell proliferation, invasiveness and response to the BRAF inhibitor (BRAFi) dabrafenib. We also preliminary assessed the potential value of circulating PTTG1 protein to monitor melanoma patient response to BRAFi or to dabrafenib plus trametinib. Dabrafenib-resistant cell lines (A375R and SK-Mel28R) were more invasive than their drug-sensitive counterparts (A375 and SK-Mel28), but expressed comparable PTTG1 levels. Dabrafenib abrogated PTTG1 expression and impaired invasion of the extracellular matrix (ECM) in A375 and SK-Mel28 cells. In contrast, it affected neither PTTG1 expression in A375R and SK-Mel28R cells, nor ECM invasion in the latter cells, while further stimulated A375R cell invasiveness. Assessment of proliferation and ECM invasion in control and PTTG1-silenced A375 and SK-Mel28 cells, exposed or not to dabrafenib, demonstrated that the inhibitory effects of this drug were, at least in part, dependent on its ability to down-regulate PTTG1 expression. PTTG1-silencing also impaired proliferation and invasiveness of A375R and SK-Mel28R cells, and counteracted dabrafenib-induced stimulation of ECM invasion in A375R cells. Further experiments performed in A375R cells indicated that PTTG1-silencing impaired cell invasiveness through inhibition of MMP-9 and that PTTG1 expression and ECM invasion could be also reduced by the CDK4/6 inhibitor LEE011. PTTG1 targeting might, therefore, represent a useful strategy to impair proliferation and metastasis of melanomas resistant to BRAFi. Circulating PTTG1 also appeared to deserve further investigation as biomarker to monitor patient response to targeted therapy.

Immunohistochemical expression of Dicer in melanoma

8591 Background: Little is known about Dicer (D) deregulation in tumour development and/or progression although several recent studies show that a decrease in D expression seems to correlate with s...