[Show abstract][Hide abstract] ABSTRACT: Solid tumor release into the circulation cell-free DNA (cfDNA) and circulating tumor cells (CTCs) which represent promising biomarkers for cancer diagnosis. Circulating tumor DNA may be studied in plasma from cancer patients by detecting tumor specific alterations, such as genetic or epigenetic modifications. Ras association domain family 1 isoform A (RASSF1A) is a tumor suppressor gene silenced by promoter hypermethylation in a variety of human cancers including melanoma. The aim of the present study was to assess the diagnostic performance of a tumor-related methylated cfDNA marker in melanoma patients and to compare this parameter with the presence of CTCs. RASSF1A promoter methylation was quantified in cfDNA by qPCR in a consecutive series of 84 melanoma patients and 68 healthy controls. In a subset of 68 cases, the presence of CTCs was assessed by a filtration method (Isolation by Size of Epithelial Tumor Cells, ISET) as well as by an indirect method based on the detection of tyrosinase mRNA by RT-qPCR. The distribution of RASSF1A methylated cfDNA was investigated in cases and controls and the predictive capability of this parameter was assessed by means of the area under the ROC curve (AUC). The percentage of cases with methylated RASSF1A promoter in cfDNA was significantly higher in each class of melanoma patients (in situ, invasive and metastatic) than in healthy subjects (Pearson chi-squared test, p
[Show abstract][Hide abstract] ABSTRACT: The occurrence of multiple primary melanomas(MPM) is quite rare with an estimated incidence ranging from 0.2% to 8.6%(Buljan M et al.2010). However, the risk of developing a primary melanoma is increased in patients with a history of a previous melanoma compared with the general population (De Giorgi et al.,2012). Between 6 and 14% of MPM cases occur in individuals with a family history of disease (Ang CG et al.1998), suggesting a genetic component in the pathogenesis of MPM. Germline mutations in the CDKN2A gene have been widely reported as the most common cause of inherited susceptibility to melanoma (Palmieri G et al., 2009). In the literature,CDKN2A germline mutations have been identified in less than 2% of single primary melanoma cases, 8 to 12% of sporadic MPM cases and 47% of MPM patients with familial melanoma (De Giorgi V et al.,2014;Puig S et al.,2005). This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: Malignant tumors of the epidermis are referred to as nonmelanoma skin cancer (NMSC). NMSC is the most frequent type of malignancy in humans and comprehends two major entities: squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). SCC arises on sun-exposed areas of the skin and mucosa but they can also occur in covered parts of the body, particularly in patients that have other predisposing factors.
[Show abstract][Hide abstract] ABSTRACT: To assess the patient's capability of performing a correct skin-check examination we investigated the association of melanoma detection pattern with Breslow thickness, by melanoma body area. In this prospective observational study, patients with primary cutaneous melanoma who presented at the Department of Dermatology at the University of Florence between January 2000 and November 2011 were interviewed as part of their clinical data recording procedure at the time of their final histopathological diagnoses of melanoma. With the aim of evaluating a self skin-check, we included patients with melanoma in the anterior part of the trunk (abdomen and chest area), which is generally considered visible in the mirror, and the posterior part of the trunk, which is a more complex area to be self-checked. The treating physician specifically questioned all patients about who had first detected or suspected the lesion that resulted in the histological diagnosis of melanoma in order to compare those who had self-detected (SD) their melanoma with those who had discovered their melanoma during a regular skin-check (RSC) with a dermatologist. A total of 186 melanoma patients were analyzed, with 67% (n=125) of melanomas located on the back and 33% (n=61) in the chest and abdominal area; the majority (55%, n=103) were in the SD group. The median Breslow thickness of the SD group was significantly greater than that of the RSC group: 0.60 versus 0.50 mm (P<0.0001). In the posterior trunk, the frequency of thick melanomas (Breslow≥1.00 mm) was significantly greater in the SD group than in the RSC group (34 vs. 11%; P=0.003), whereas there was no difference in the frequency of thick melanoma by detection patterns in the anterior trunk. Given the influence of the body area in detecting threatening melanoma, we should encourage people to obtain dermatological skin-checks more often. Skin self-examinations cannot be sufficiently accurate.
Full-text · Article · Oct 2014 · European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP)
[Show abstract][Hide abstract] ABSTRACT: An 85-year-old woman presented with a lesion on the sole of her right foot, which was histologically confirmed as acral lentiginous melanoma. Because of the large field involved and because the patient refused any invasive or painful treatment, topical treatment with imiquimod was commenced. At the 20-month follow-up, the patient was still continuing treatment with topical imiquimod, and no metastases to the lymph nodes or viscera were found, either clinically or in imaging studies. We believe that the success of the treatment cannot be explained only by the stimulation of the immune system induced by imiquimod. A possible explanation might be ‘tumour dormancy’, where a tumour grows very slowly because of a balance between the neoplasia and the immune (and nonimmune) mechanisms of tumour control. The use of imiquimod has so far allowed our patient to avoid surgery, and perturbation of the mechanisms of tumour regulation, such as local immunity and angiogenesis, has not taken place.
No preview · Article · Sep 2014 · Clinical and Experimental Dermatology
[Show abstract][Hide abstract] ABSTRACT: To verify preliminary studies on patients with melanoma exposed to β-blockers that suggested a reduced risk of disease recurrence and death.
Data were obtained from all consecutive patients diagnosed as having melanoma between January 1, 1993, and December 31, 2009, at the Department of Dermatology of the University of Florence, Azienda Sanitaria di Firenze. Participants were excluded if at baseline they reported a previous diagnosis of cutaneous malignant melanoma or another malignant disease. We also excluded participants with evidence of visceral, lymph nodal, and in-transit metastasis at the time of the diagnosis.
Of 741 consecutive patients with melanoma, 79 (11%) were prescribed β-blockers (for hypertension in most cases) for 1 or more years (treated) and 662 (89%) were not (untreated). The multivariate Cox model indicated that the treated group had improved overall survival after a median follow-up of 4 years (P=.005). For each year of β-blocker use, the risk of death was reduced by 38%. The presence of hypertension, the use of antihypertensive agents for 1 or more years, or the use of other commonly used medicines were not associated with a better outcome for patients with melanoma.
The results confirm and strengthen previous findings that β-blocker use is associated with a reduced risk of melanoma recurrence and death. The results also indicate the strong need for a randomized clinical trial to conclusively assess whether β-blockers afford protection against melanoma recurrence and death.
Full-text · Article · Nov 2013 · Mayo Clinic Proceedings
[Show abstract][Hide abstract] ABSTRACT: The number needed to excise (NNE) is a metric used to convey the efficiency of dermatological practice by serving as a gauge for the diagnostic accuracy of melanoma. Rather than an NNE for melanoma alone, we assert that the NNE should measure all skin cancer types and we present data on NNE from two clinical sites demonstrating the utility and trends in NNE over time.
No preview · Article · Apr 2013 · Australasian Journal of Dermatology
[Show abstract][Hide abstract] ABSTRACT: Excess body weight has been shown to increase the risk for development of several common cancers, such as postmenopausal breast, colon, endometrium, kidney, and esophagus cancers. The main aim of the present study was to investigate the potential relationship between excess body weight, assessed in terms of BMI, and Breslow thickness in 605 patients affected by primary cutaneous melanoma. Particularly, we evaluated the occurrence of thick melanoma (>1 mm) in overweight compared with nonoverweight patients. The effect of BMI (≥25 vs. <25 kg/m) on the risk of having a diagnosis of thick melanoma was estimated in terms of odds ratio (OR) by logistic regression analysis, adjusted for age, sex, and histological type. Significant differences in overweight versus nonoverweight patients were found with respect to sex distribution. In fact, the occurrence of thick melanoma was greater in overweight women than in nonoverweight women (OR=1.64). When the analysis was restricted to postmenopausal women, the corresponding OR increased further to 2.50. In conclusion, a positive association between excess body weight and the risk of thick melanoma was found only in female patients. On stratifying patients into subgroups, the relationship between the risk of being diagnosed with a thick melanoma (>1.0 mm) and overweight status (BMI≥25 kg/m) was significantly affected by both sex and menopausal status. Despite limitations because of both the study design and the relatively small numbers of patients in certain subgroups, overweight status may be associated with an increased Breslow thickness in postmenopausal women.
No preview · Article · Mar 2013 · European journal of cancer prevention: the official journal of the European Cancer Prevention Organisation (ECP)
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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-AR pathway in melanoma patients. Questions regarding the type of β-blocker or tumor characteristics, appropriate treatment paradigms and, most importantly, efficacy must be answered in randomized clinical studies before β-blockers can be considered a therapeutic option for patients with melanoma.
No preview · Article · Nov 2012 · Expert Review of Anti-infective Therapy
[Show abstract][Hide abstract] ABSTRACT: Background: oncological research has been focused on evaluating estrogen receptors (ERs) in estrogen-related tumors and understanding the potential role of ERs in the pathophysiology of cancer. Objectives: To investigate the significance of estrogen receptor beta (ERβ) in melanoma. Methods: We prospectively evaluated ERβ expression in malignant melanoma (MM) tissue and adjacent healthy skin by quantitative immunohistochemistry at the Department of Dermatology of the University of Florence from 1998 to 2010. Results: ERβ was detected with varying staining intensity in the 66 malignant melanocytic lesions. After adjusting for age and gender, we found that ERβ expression was significantly lower in melanoma tissue compared with adjacent healthy skin (P < 0.0001). We also found significantly lower ERβ levels in thick melanoma tissue compared with thin melanoma tissue. In addition, there was a positive association between Breslow thickness and the difference of ERβ expression between healthy tissue and melanoma tissue (P = 0.0004). Consistent with gender differences in melanoma survival, men showed significantly lower levels of ERβ than women in both melanoma and healthy tissues (P = 0.05 and 0.02, respectively). Conclusions: ERβ expression is inversely associated with Breslow thickness and also significantly influenced by gender in MM.
Full-text · Article · Sep 2012 · British Journal of Dermatology
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] 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 (F&N) and the scalp separately. We carried out a retrospective analysis of 757 melanoma patients. In particular, we studied the prognostic impact of different melanoma skin localizations (head and neck, trunk, upper extremities and lower extremities). Afterwards, we divided HNM into two subgroups, F&N and scalp, to evaluate their impact in the HNM prognosis. Data showed a significantly lower 5-year overall survival probability for HNM (78.9 versus 93.1% for other body sites; 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.
No preview · Article · Aug 2012 · Melanoma research
[Show abstract][Hide abstract] ABSTRACT: Objective:
The aim of this retrospective study was to analyze the relationship between detection pattern, tumor thickness, patient demographics, and personal and family history of melanoma in the era of noninvasive diagnosis.
All patients with primary cutaneous melanoma who presented to the Department of Dermatology at the University of Florence between January 2000 and November 2010 were interviewed at the time of their final histopathological diagnoses of melanoma as part of their clinical record. The treating physician specifically questioned all patients about who had first detected or suspected the lesion that resulted in the histological diagnosis of melanoma.
A total of 802 melanoma patients were analyzed. The spouse found approximately 16% of the melanomas, and a similar percentage was discovered by the general practitioner. The largest group of melanomas (36%) was discovered during regular annual skin examinations by dermatologists, while another large group (33%) were discovered by the patients themselves. The data that emerged from our study is that self-detection was associated with a greater probability of having a thick melanoma and, therefore, a poor prognosis (odds ratio 1.56).
Because the current mortality of melanoma is still stable, we are convinced that a new message should be introduced to encourage high-risk patients to have an annual skin examination as a rule.
[Show abstract][Hide abstract] 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.
No preview · Article · Jul 2012 · Dermatologic Therapy
[Show abstract][Hide abstract] 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.
No preview · Article · Mar 2012 · Melanoma research