Showing papers by "Marta Grazzini published in 2012"

Multiparametric analysis of cell-free DNA in melanoma patients.

Abstract: Cell-free DNA in blood (cfDNA) represents a promising biomarker for cancer diagnosis. Total cfDNA concentration showed a scarce discriminatory power between patients and controls. A higher specificity in cancer diagnosis can be achieved by detecting tumor specific alterations in cfDNA, such as DNA integrity, genetic and epigenetic modifications. The aim of the present study was to identify a sequential multi-marker panel in cfDNA able to increase the predictive capability in the diagnosis of cutaneous melanoma in comparison with each single marker alone. To this purpose, we tested total cfDNA concentration, cfDNA integrity, BRAFV600E mutation and RASSF1A promoter methylation associated to cfDNA in a series of 76 melanoma patients and 63 healthy controls. The chosen biomarkers were assayed in cfDNA samples by qPCR. Comparison of biomarkers distribution in cases and controls was performed by a logistic regression model in both univariate and multivariate analysis. The predictive capability of each logistic model was investigated by means of the area under the ROC curve (AUC). To aid the reader to interpret the value of the AUC, values between 0.6 and 0.7, between 0.71 and 0.8 and greater than 0.8 were considered as indicating a weak predictive, satisfactory and good predictive capacity, respectively. The AUC value for each biomarker (univariate logistic model) was weak/satisfactory ranging between 0.64 (BRAFV600E) to 0.85 (total cfDNA). A good overall predictive capability for the final logistic model was found with an AUC of 0.95. The highest predictive capability was given by total cfDNA (AUC:0.86) followed by integrity index 180/67 (AUC:0.90) and methylated RASSF1A (AUC:0.89). An approach based on the simultaneous determination of three biomarkers (total cfDNA, integrity index 180/67 and methylated RASSF1A) could improve the diagnostic performance in melanoma.

The prognostic impact of the anatomical sites in the 'head and neck melanoma': scalp versus face and neck.

Abstract: Cutaneous melanoma is a malignant neoplasia with several demographic and histopathological prognostic factors. Many studies stress that the head and neck region has a worse prognosis compared with other localizations, but the reasons for this worse prognosis are unclear. Therefore, the aim of our study is to analyse the poor prognosis of head and neck melanoma (HNM) with respect to the other anatomical sites, considering the face and neck (FN P=0.05). Moreover, on analysing the two anatomical areas considered among HNM, we observed a 5-year overall survival of 81.8% for F&N and 66.7% for scalp. HNM has different and worse prognostic features with respect to other sites, but this trend is not only because of scalp melanoma but is also determined by F&N melanoma, which we believe to be underestimated until now.

Is skin self-examination for cutaneous melanoma detection still adequate? A retrospective study.

Abstract: Objective: The aim of this retrospective study was to analyze the relationship between detection pattern, tumor thickness, patient demographics, and personal and

Dermoscopy, confocal laser microscopy, and hi-tech evaluation of vascular skin lesions: diagnostic and therapeutic perspectives.

Abstract: Vascular skin lesions comprise a wide and heterogeneous group of malformations and tumors that can be correctly diagnosed based on natural history and physical examination. However, considering the high incidence of such lesions, a great number of them can be misdiagnosed. In addition, it is not so rare that an aggressive amelanotic melanoma can be misdiagnosed as a vascular lesion. In this regard, dermoscopy and confocal laser microscopy examination can play a central role in increasing the specificity of the diagnosis of such lesions. In fact, the superiority of these tools over clinical examination has encouraged dermatologists to adopt these devices for routine clinical practice, with a progressive spread of their use. In this review, we will go through the dermoscopic and the confocal laser microscopy of diagnosis of most frequent vascular lesions (i.e., hemangiomas angiokeratoma, pyogenic granuloma, angiosarcoma) taking into particular consideration the differential diagnosis with amelanotic melanoma.

Features of small melanocytic lesions: does small mean benign? A clinical-dermoscopic study.

Abstract: The use of dermoscopy is known to increase the sensitivity and specificity in the clinical diagnosis of cutaneous pigmented melanocytic lesions compared with naked-eye examinations. However, small pigmented melanocytic lesions with maximum clinical diameters of 6 mm remain the most significant diagnostic challenge to the clinician, particularly in the diagnosis of small melanoma, both in naked-eye and in dermatoscopic examinations. The aim of the present study was to analyze the clinical and dermatoscopic features of small pigmented melanocytic lesions, focusing on more frequently occurring features in small melanoma to identify them earlier. A total of 103 pigmented melanocytic lesions with diameters less than 6 mm were analyzed. On histopathological examination, 34 of these lesions were diagnosed as melanomas and the remaining lesions (n = 69) were diagnosed as benign, melanocytic lesions. Images of cases were independently and blindly administered to three dermatologist experts in dermoscopy, who were asked to examine the clinical and dermatoscopic images of melanocytic skin lesions separately and to fill out a printed questionnaire to rate the images according to the ABCD clinical criteria and according to typical dermoscopic pattern analyses. The results of the questionnaires were then analyzed and crossed in order to rate the clinical and dermoscopic features of small pigmented lesions. Our study proved that the clinical criteria for diagnosing melanoma are not as reliable in the diagnosis of pigmented lesions of less than 6 mm diameter. However, the use of dermoscopy, even if not nullifying, allows a better classification of small, melanocytic lesions through pattern analysis.

Epidemiology of melanoma: is it still epidemic? What is the role of the sun, sunbeds,Vit D, betablocks, and others?

Abstract: The incidence of cutaneous malignant melanoma is continuously increasing worldwide, but only minimal changes in mortality have been observed. This phenomenon has brought into question whether this increased incidence reflects a true or apparent melanoma epidemic. The most recent data suggest that this epidemiological trend may be explained by the existence of a certain degree of melanoma overdiagnosis, especially of thin lesions, which probably would never progress to advanced disease if left untreated. However, acute sun exposure and widespread use of sunbeds may also justify the increase in melanoma incidence. Recently, both vitamin D and beta-blocker use seem to play a beneficial role in melanoma progression.

β-adrenergic-blocking drugs and melanoma: Current state of the art

Abstract: The purpose of this review is to present the preclinical, epidemiological and clinical data relevant to the association between β-blockers and melanoma progression. Preclinical studies have shown that β-adrenergic receptor (β-AR) signaling can inhibit multiple cellular processes involved in melanoma progression and metastasis. These observations have suggested the possibility that drugs originally intended for the treatment of cardiovascular disease, the β-AR blockers, may provide new therapeutic opportunities for the control of tumor progression. A large number of observational studies demonstrated the protective effect of β-blockers in breast cancer but, more recently, similar findings were also reported in other cancers such as prostate cancer and melanoma. With regard to melanoma, two recently published studies demonstrated a great reduction in the risk of disease progression for each year of treatment with β-blockers. The results from these studies have suggested a potential role for targeting the β-...

Obesity and melanoma.

Abstract: MADAM, Shipman and Millington have properly explored the association of obesity, the biggest health problem of our times, with skin diseases. Because of the worldwide increasing incidence of malignant melanoma (MM), in oncology research, increasing attention has been focused on the potential role of changing lifestyle factors, particularly with obesity and diet. Although, as stated by the authors, the links between obesity and melanoma remain largely unexplored, population-based epidemiological studies have lately emerged providing plausible evidence for a link between obesity and MM. Brandon et al. found that obesity causes rapid melanoma growth by promoting angiogenesis in obese mice. Mechanisms that link excess weight and cancer risk are not fully understood and are still more unclear in MM than in other neoplasms. The authors have mentioned the leptin pathway without elucidating the biological basis of such a relationship. At least four different mechanisms seem to be involved in the association between excess body weight and MM risk. Firstly, obesity provides multiple hormonal and metabolic changes through three hormone systems, including the insulin and insulin-like growth factor (IGF) axis, sex steroids and adipokines. Chronic hyperinsulinaemia, a consequence of insulin resistance in the obese, increases IGF-1 bioavailability, which, in turn, favours tumour growth by inhibiting apoptosis and stimulating cell proliferation in the so-called insulin-cancer hypothesis. In this regard, hyperglycaemia, independently from body mass index (BMI), has been associated with a twofold increase of MM risk. With regard to the relationship between obesity and sex steroids, hyperinsulinaemia and elevated IGF-1 result in reduced hepatic synthesis of sex hormone-binding globulin (SHBG), therefore allowing greater bioavailability of free oestrogen. In addition, among overweight individuals there is an increased peripheral conversion of androgens to oestrogens in fat tissue. Thus, given that the presence of oestrogen receptors in melanocytes has been demonstrated, we cannot rule out that increased plasma oestrogen levels in obese individuals might contribute to enhance tumour growth in MM, as already observed in breast cancer. Secondly, leptin, an insulin-sensitizing adipokine which is produced mainly from visceral fat adipocytes in proportion to the mass of adipose tissue, causes inflammation, cell proliferation and angiogenesis. In MM, leptin accelerates in vivo tumour growth and increases tumour angiogenesis by interacting with angiogenic factors, such as vascular endothelial growth factor (VEGF), which are upregulated in MMs from obese mice. Moreover, MM risk was found to be positively associated with serum leptin levels in a recent epidemiological study. Thirdly, caveolin-1 (Cav-1), a protein involved in the organization and remodelling of the extracellular matrix, has been directly correlated with tumour growth, aggressiveness and progression of MM. Recently, a study has clearly evidenced that Cav-1 expression is significantly influenced in vivo by diet-induced obesity. Fourthly, BMI is inversely associated with serum vitamin D levels, which are related with MM risk and outcome. Indeed, lower serum 25(OH)D3 levels were found in patients with MM compared with the control group. Furthermore, higher serum 25(OH)D3 levels, at MM diagnosis, were associated with both thinner lesions and better survival from MM, suggesting a role for vitamin D in MM outcome. Finally, further plausible carcinogenic mechanisms of obesity include long-term storage of toxins, medications and vitamins in adipose tissue, which can serve as a continuous source of carcinogens. Therefore, the pathophysiology of obesity is complex and multifactorial, and thus, it is unlikely that ‘one size fits all’. We believe that all these mechanisms can coexist and play not mutually exclusive functions in increasing MM risk among obese individuals. If obesity is going to be consistently reported as a modifiable risk factor for MM, given the high prevalence of obesity in developed countries, more intervention research on the prevention and treatment of obesity may be another essential component of future research in primary prevention of melanoma, having a strong impact on MM diagnosis and prognosis.

I β-bloccanti: nuova prospettiva terapeutica per il melanoma

Abstract: Riassunto. Recenti evidenze della ricerca di base hanno avanzato teorie innovative riguardanti il ruolo del sistema neuroendocrino sul microambiente tumorale e metastatico. Queste osservazioni hanno infatti suggerito la possibilita che farmaci originariamente destinati al trattamento di altre malattie, ed in particolare i bloccanti dei recettori β-adrenergici (β-bloccanti) utilizzati nelle malattie cardiovascolari, potrebbero fornire nuove opportunita terapeutiche per il controllo della progressione dei tumori. Un importante numero di studi osservazionali ha evidenziato l’effetto protettivo dei β-bloccanti nel carcinoma della mammella e, piu recentemente, risultati simili sono stati riportati anche per altri tipi di tumore, quali il carcinoma della prostata ed il melanoma. I risultati di questi studi hanno evidenziato che l’utilizzo dei β-bloccanti, ma non di altri farmaci antiipertensivi, era associato ad un notevole allungamento del periodo libero da malattia e della sopravvivenza globale. Per quanto concerne il melanoma, un recente studio di De Giorgi et al. ha evidenziato una riduzione del 36% del rischio di progressione di malattia per ogni anno di assunzione di β-bloccanti. Questi dati, originati da studi osservazionali, non possono essere considerati conclusivi e, prima di passare alla eventuale cura dei pazienti, necessitano di validazione per mezzo di studi sperimentali che sono in corso di svolgimento. Parole chiave. β-bloccanti, carcinoma della prostata, melanoma, ipertensione arteriosa, propranololo. β-blockers: a new and emerging treatment for melanoma. Summary. Recent studies have underlined the innovative theories concerning the role of neuroendocrine system on the tumor and metastasis microenvironment. These observations have suggested the possibility that drugs originally intended for the treatment of cardiovascular disease, the β-adrenergic receptor blockers (β-blockers), may provide new therapeutic opportunities for the control of tumor progression. A large number of observational studies showed the protective effect of β-blockers in breast cancer, but more recently, similar findings were also reported in other cancers such as prostate cancer and melanoma. The results of these studies have shown that the use of β-blockers, but not other antihypertensive drugs, was associated with a significant increase of the disease free survival and of the overall survival. With regard to melanoma, a recent study by De Giorgi et al. showed a 36% reduction in risk of disease progression for each year of treatment with β-blockers. These data, originating from prospective studies, cannot be considered conclusive and require validation by means of clinical trials that are underway.

The "golden brown halo" of the Miescher nevus.

Abstract: T HE MIESCHER NEVUS (MN) IS A RELATIVELY firm, brownish to skin-colored, domeshaped, roundish papule that occurs most commonly on the head and neck. It is not uncommon for a terminal hair to emanate from an MN. The MN tends to be quite stable, with little to no change detected during follow-up. The diagnosis of MN is usually easy to make based on the clinical morphological appearance; however, on occasion, it may be difficult to differentiate an MN from a basal cell carcinoma (BCC), especially because dermoscopy can reveal arborizing vessels in both lesions. To our knowledge, this is the first report of a dermoscopic pattern consisting of a golden brown halo that we have observed surrounding many MN (Figure, A, B, and C). This golden brown halo is not seen in BCC (Figure, D). In our experience, the golden halo may be an additional dermoscopic feature that can help differentiate an MN from a BCC.

Pigmented lesions in the oral mucosa: the ugly but good

Abstract: A 52-year-old man with a history of a malignant melanoma of the scalp was referred to us from a dentist with the suspected diagnosis of oral melanoma. Clinically, we observed a 5-mm blue–grayish macula on the oral mucosa localized under …