Publications (41)133.8 Total impact
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Dataset: Dermoscopy of facial AK IEC and SCC
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Article: Linking αMSH with PPARγ in B16-F10 melanoma.
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ABSTRACT: We have discovered a new α-melanocyte stimulating hormone (α-MSH)/peroxisome proliferator activated receptor-γ (PPAR-γ) connection in B16-F10 cells. Both PPAR-γ up-regulation and its induction as an active transcription factor were observed in response to α-MSH. The α-MSH/PPAR-γ connection influenced both pigmentation and proliferation. The forskolin-stimulated cAMP/PKA pathway was not able to induce either PPAR-γ translocation into the nucleus or PPAR-γ transcriptional activity. As the melanocortin-1 receptor, the specific receptor for the α-MSH, is a G-protein coupled receptor, we wondered whether the phosphatidylinositol [PI(4,5)P(2) /PLC(β) ] signal pathway was involved in mediating the α-MSH-dependent PPAR-γ activation. Employing inhibitors of PI(4,5)P(2) /PLC(β) pathway, the results of our experiments suggested that this pathway was promoted by α-MSH and that α-MSH played a role in mediating PPAR-γ activation. We have demonstrated, for the first time, that α-MSH induces the PI(4,5)P(2) /PLC(β) pathway, through analysis of the basic steps of the pathway. The α-MSH effect on PPAR-γ was independent of animal species and was not correlated with the physio-pathological status.Pigment Cell & Melanoma Research 08/2012; · 5.06 Impact Factor -
Article: Reflectance confocal microscopy for the evaluation of solitary red nodules.
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ABSTRACT: The correct assessment of a solitary red nodule in clinical practice is of crucial importance, amelanotic melanoma being the most important differential diagnosis. Dermoscopy is nowadays a pivotal tool in the management of skin tumors, however it has some limitations in the evaluation of nonpigmented lesions, in which the diagnosis is merely based on the evaluation of the vascular pattern. Recently, reflectance confocal microscopy has been introduced as a new, noninvasive technique for the diagnosis of skin lesions. Confocal microscopy provides skin imaging in vivo at cellular level resolution, close to conventional histology. We present a series of clinical scenarios of red nodules, including melanoma metastasis, pyogenic granuloma, eccrine poroma, Spitz nevus and dermatofibroma. Reflectance confocal microscopy examination added important information to the clinical diagnosis and subsequent management in all cases except for dermatofibroma. We discuss the advantages and limitations of this technique in this particular field of application.Dermatology 06/2012; 224(4):295-300. · 2.05 Impact Factor -
Article: Dermoscopy and confocal microscopy of thrombosed hemangiomas.
Archives of dermatology 03/2012; 148(3):410. · 4.76 Impact Factor -
Article: Analysis of the miR-34a locus in 62 patients with familial cutaneous melanoma negative for CDKN2A/CDK4 screening.
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ABSTRACT: MicroRNAs are small non-coding RNAs, which inhibit expression of specific target genes at the post-transcriptional level and are often misregulated in human cancer. Among them, miR-34a is considered a tumor suppressor with a hypothetical role in melanoma tumorigenesis. In this work, 62 Italian index patients with familial melanoma and negative for CDKN2A/CDK4 screening were investigated for miR-34a germline mutations. Eight novel miR-34a sequence variants were identified at both the heterozygous (c.+259G>A, c.+424G>A, c.+1465C>T, c.+1769C>T, c.+2456T>G, c.+2603C>T, c.+2972T>A, c.+3069T>C) and homozygous (c.+424G>A, c.+1465C>T, c.+1769C>T) states. Molecular screening identified all nucleotide changes in a healthy population of 150 controls and demonstrated that they are common polymorphisms. However, statistically significant differences of allele and genotype frequencies were detected for c.+1465C>T and c.+1769C>T, and borderline values for c.+2456T>G. By stratifying patients by relevant clinical features (presence/absence of multiple primary melanoma, Breslow's thickness, phototype and number of nevi), no significant findings were noted except for an association between the c.+424G>A (heterozygous individual GA) and multiple primary melanoma and phototype III-IV. Our preliminary study suggests that miR-34a, although having a role in late tumorigenesis, does not contribute to the inherited susceptibility to cutaneous melanoma. A function as phenotypic modulator in familial melanoma cannot be excluded.Familial Cancer 12/2011; 11(2):201-8. · 1.30 Impact Factor -
Article: Human Papillomaviruses, p16INK4a and Akt expression in basal cell carcinoma.
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ABSTRACT: The pathogenic role of beta-HPVs in non melanoma skin cancer (NMSC), is not still completely understood, and literature data indicate that they might be at least cofactors in the development of certain cutaneous squamous cell carcinomas. However, only few reports contain data on basal cell carcinoma (BCC). The HPVs interact with many cellular proteins altering their function or the expression levels, like the p16INK4a and Akt. Our study aimed to determine the presence of different beta -HPV types and the expression of p16INK4a and Akt in BCC, the commonest NMSC, in the normal appearing perilesional skin and in forehead swab of 37 immunocompetent patients. The expression of p16INK4a and Akt, by immunohistochemistry, and the HPV DNA, by nested PCR, were investigated in each sample. No correspondence of HPV types between BCC and swab samples was found, whereas a correspondence between perilesional skin and BCC was ascertained in the 16,7% of the patients. In BCC, 16 different types of beta HPV were found and the most frequent types were HPV107 (15,4%), HPV100 (11,5%) and HPV15 (11,5%) all belonging to the beta HPV species 2. Immunohistochemistry detected significant p16INK4a expression in almost all tumor samples (94,3%) with the highest percentages (> 30%) of positive cells detected in 8 cases. A statistically significant (p = 0,012) increase of beta HPV presence was detected in p16INK4a strongly positive samples, in particular of species 2. pAkt expression was detected in all tumor samples with only 2 cases showing rare positive cells, whereas Akt2 expression was found in 14 out of 35 BCC (40%); in particular in HPV positive samples over-expressing p16INK4a. Our data show that p16INK4a and pAkt are over-expressed in BCC and that the high expression of p16INK4a and of Akt2 isoform is often associated with the presence of beta-HPV species 2 (i.e. HPV 15). The association of these viruses with the up-regulation of p16INK4a and Akt/PI3K pathway suggests that in a subtype of BCC these viruses may exert a role in the carcinogenesis or in other, still undefined, biological property of these tumors. If this particular type of BCC reflects a different biology it will remain undisclosed until further studies on a larger number of samples will be performed.Journal of Experimental & Clinical Cancer Research 11/2011; 30:108. · 2.15 Impact Factor -
Article: Clinical features predicting identification of CDKN2A mutations in Italian patients with familial cutaneous melanoma.
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ABSTRACT: CDKN2A is the most common, most penetrant gene whom germline mutations predisposing to cutaneous familial melanoma (FAM). Multiple primary melanoma (MPM), early age at onset, >2 affected members and pancreatic cancer are consistent features predicting positive test. However, the impact that cumulative clinical features have on the likelihood of molecular testing is unknown. In this work, genotype-phenotype correlations focused on selected clinical features were performed in 100 Italian FAM unrelated patients. Molecular studies of CDKN2A mutations were performed by direct sequencing. Statistical study included multiple correspondence analysis, uni- and multivariate analyses, and individual patient's probability calculation. MPM, >2 affected family members, Breslow thickness >0.4mm, and age at onset ≤41 years were the unique independent features predicting positive CDKN2A screening. The rate of positive testing ranged from 93.2% in the presence of all of them, to 0.4% in their absence. The contribution of each of them was quantified accordingly, with MPM being the most significant. These findings confirm previous data and add novel insights for the role of accurate patients' selection in CDKN2A screening.Cancer epidemiology. 09/2011; 35(6):e116-20. -
Article: Lichenoid keratosis-like melanomas.
Journal of the American Academy of Dermatology 09/2011; 65(3):e85-7. · 3.99 Impact Factor -
Article: Dermatoscopy of facial actinic keratosis, intraepidermal carcinoma, and invasive squamous cell carcinoma: a progression model.
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ABSTRACT: Little is known about the dermoscopic features of keratinocyte skin cancer. We sought to determine the dermoscopic features of facial actinic keratosis (AK), intraepidermal carcinoma (IEC), moderately to poorly differentiated invasive squamous cell carcinoma (SCC), and well-differentiated SCC of the keratoacanthoma type. This was a retrospective analysis of dermoscopic images of histopathologically diagnosed keratinocyte skin cancer. A total of 243 (70 AK, 71 IEC, 78 SCC, and 24 keratoacanthomas) tumors of the face from 243 patients (mean age: 71.1 years; range: 44-94 years) were analyzed. The majority of patients had a fair skin type, history of melanoma or nonmelanoma skin cancer, and multiple AK. A red pseudonetwork was significantly associated with AK (P < .001), whereas dotted/glomerular vessels, diffuse yellow opaque scales, and microerosions were significantly more prevalent among IEC (P < .001). Hairpin vessels, linear-irregular vessels, targetoid hair follicles, white structureless areas, a central mass of keratin, and ulceration were significantly associated with invasive SCC (P < .001 for all criteria). Similar patterns as in SCC were observed among keratoacanthomas. The retrospective design of our study and the lack of assessment of sensitivity and specificity of the dermoscopic criteria are limitations. Based on our findings we propose a progression model of facial AK developing into IEC and invasive SCC.Journal of the American Academy of Dermatology 08/2011; 66(4):589-97. · 3.99 Impact Factor -
Article: Total body skin examination for skin cancer screening in patients with focused symptoms.
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ABSTRACT: The value of total body skin examination (TBSE) for skin cancer screening is controversial. We sought to determine whether TBSE could be helpful in patients with focused skin symptoms who would not otherwise have undergone TBSE. In a prospective, multicenter, cross-sectional study consecutive adult patients were recruited during a period of 18 months. Physicians first inspected problem areas and uncovered areas and then performed TBSE. Equivocal lesions detected in both steps were excised or biopsied. Primary outcomes were the absolute and relative risks of missing skin cancer and the number of patients needed to examine to detect melanoma or another malignancy. A secondary outcome was the proportion of false-positive results obtained by TBSE. We examined 14,381 patients and detected 40 (0.3%) patients with melanoma and 299 (2.1%) with at least one nonmelanoma skin cancer by TBSE. In 195 (1.3%) patients equivocal lesions found by TBSE turned out to be benign. We calculated that 47 patients need to be examined by TBSE to find one skin malignancy and 400 patients to detect one melanoma. The risk of missing one malignancy if not performing TBSE was 2.17% (95% confidence interval 1.25-3.74). Factors significantly increasing the chance to find a skin cancer were age, male gender, previous nonmelanoma skin cancer, fair skin type, skin tumor as the reason for consultation, and presence of an equivocal lesion on problem/uncovered areas. The impact of TBSE on skin cancer mortality was not evaluated. TBSE improves skin cancer detection in patients with focused skin symptoms and shows a low rate of false-positive results.Journal of the American Academy of Dermatology 07/2011; 66(2):212-9. · 3.99 Impact Factor -
Article: Frequency of dermoscopic nevus subtypes by age and body site: a cross-sectional study.
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ABSTRACT: To subclassify acquired nevi by dermoscopic pattern. Cross-sectional study with consecutive enrollment. Pigmented lesion clinics in referral academic medical centers. Individuals older than 2 years undergoing total skin examination were consecutively recruited between October 1, 2008, and May 31, 2009, and, based on their age, assigned to 1 of 8 groups. For each patient, the location and dermoscopic pattern of all nevi on the torso were recorded. Nevi were dermoscopically subclassified as globular, reticular, mixed (reticular-globular) pattern with peripheral or central globules, or unspecified pattern. Frequency of dermoscopic nevus subtypes stratified by patient age and location of the nevi. A total of 5481 nevi in 480 individuals were evaluated. The number of all nevus subgroups, except for unspecified pattern nevi, significantly increased before and decreased after the fourth decade of life. Globular nevi were most prevalent on the upper trunk in children and adolescents; the number decreased consistently after the second decade of life. The reticular pattern was the most common nevus pattern after the second decade of life and the most common nevus subgroup on the upper and middle back. Although uncommon, central globular nevi also showed an age-dependent trend, similar to that of reticular nevi. Nevi with the peripheral globular pattern declined rapidly after the third decade of life and were no longer observed after the sixth decade. The number of unspecified pattern nevi was stable across all age groups. Age, dermoscopic pattern, and location of nevi should be jointly considered when evaluating melanocytic lesions.Archives of dermatology 06/2011; 147(6):663-70. · 4.76 Impact Factor -
Article: Adjuvant treatment with topical 5% imiquimod cream for resected stage IIIb melanoma.
European journal of dermatology: EJD 04/2011; 21(3):410-1. · 2.53 Impact Factor -
Article: Dermoscopy of pigmented lesions of the vulva: a retrospective morphological study.
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ABSTRACT: The dermoscopic patterns of pigmented skin tumors are influenced by the body site. To evaluate the clinical and dermoscopic features associated with pigmented vulvar lesions. Retrospective analysis of clinical and dermoscopic images of vulvar lesions. The χ² test was used to test the association between clinical data and histopathological diagnosis. A total of 42 (32.8%) melanocytic and 86 (67.2%) nonmelanocytic vulvar lesions were analyzed. Nevi significantly prevailed in younger women compared with melanomas and melanosis and exhibited most commonly a globular/cobblestone (51.3%) and a mixed (21.6%) pattern. Dermoscopically all melanomas showed a multicomponent pattern. Melanotic macules showed clinical overlapping features with melanoma, but their dermoscopic patterns differed significantly from those observed in melanomas. The diagnosis and management of pigmented vulvar lesions should be based on a good clinicodermoscopic correlation. Dermoscopy may be helpful in the differentiation of solitary melanotic macules from early melanoma.Dermatology 02/2011; 222(2):157-66. · 2.05 Impact Factor -
Article: AXIN2 germline mutations are rare in familial melanoma.
Genes Chromosomes and Cancer 02/2011; 50(5):370-3. · 3.31 Impact Factor -
Article: Dermoscopy of patients with multiple nevi: Improved management recommendations using a comparative diagnostic approach.
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ABSTRACT: To assess the outcome on management recommendations of a comparative approach vs a morphologic approach in evaluating dermoscopic images of lesions from a series of patients with multiple nevi. In a 2-step study, 6 experienced dermoscopists were asked to provide management recommendations (excision or follow-up) for a series of lesions from patients with multiple nevi based on dermoscopic images of the lesions. In the first step, participating dermoscopists evaluated individual images of lesions based only on morphologic structure (morphologic approach). In the second step, the same lesions were grouped by patient, allowing the participants to evaluate the lesions in the context of other nevi from the same patient (comparative approach). Academic referral center. Seventeen patients with 190 lesions (184 monitored nevi, 4 excised nevi, and 2 excised melanomas). Using pooled data from each step, excision recommendation rates for the comparative approach and the morphologic approach were calculated. Using the morphologic approach, 55.1% of overall recommendations favored excision; using the comparative approach, the rate decreased to 14.1%. The 2 melanomas included in the study were correctly judged to merit excision by all participants in step 1 and in step 2. Conclusion Among patients with multiple nevi, evaluation of equivocal lesions in the context of a patient's other nevi results in a lower rate of excision recommendations compared with evaluation of individual lesions based on morphologic structure alone.Archives of dermatology 01/2011; 147(1):46-9. · 4.76 Impact Factor -
Article: What dermoscopy tells us about nevogenesis.
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ABSTRACT: The evolution of nevi is a complex process involving several constitutional and environmental factors. Although histopathology is the gold standard for the diagnosis and classification of melanocytic nevi, the widespread use of in vivo diagnostic technologies such as dermoscopy and more recently of reflectance confocal microscopy, has enriched profoundly our knowledge regarding the morphological variability of nevi in different stages of their evolution. In addition, significant progress has been made in our understanding of genetic alterations and molecular pathways involved in the formation of melanocytic tumors. All this newly acquired knowledge increasingly questions whether morphologically different nevi are also histiogenetically different. In this article, we intend to extract some of the salient points from published clinical and molecular studies on melanocytic tumors and attempt to assimilate them into an integrative concept of nevogenesis.The Journal of Dermatology 01/2011; 38(1):16-24. · 1.49 Impact Factor -
Article: Wnt/β-catenin signaling is stimulated by α-melanocyte-stimulating hormone in melanoma and melanocyte cells: implication in cell differentiation.
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ABSTRACT: Wnt/β-catenin signaling plays important roles in many developmental processes including neural crest-derived melanocyte development and migration. However, the effective contribution of Wnt/β-catenin pathway in melanogenesis in adult human melanocytes has not been fully elucidated. Here, we report that in melanoma cells and in normal human melanocytes, melanogenesis stimulation by α-melanocyte-stimulating hormone (α-MSH) induces phosphorylation of β-catenin-Ser675 and stabilization of β-catenin protein. Activation of protein kinase A by α-MSH attenuates glycogen synthase kinase-3β, which regulates ubiquitin-dependent degradation of β-catenin, suggesting a coordinated mechanism of β-catenin activity stimulation. Consistent with increased nuclear β-catenin, cyclic adenosine monophosphate (cAMP) elevation facilitates β-catenin-dependent transactivation of many Wnt target genes. Moreover, chromatin immunoprecipitation assays demonstrated an increased association of β-catenin with the proximal promoter of microphthalmia-associated transcription factor, the master regulator of pigmentation. These results demonstrate the existence of cross talk between the cAMP and Wnt pathways in melanocytes, suggesting that β-catenin could play a key role in the physiological regulation of epidermal melanogenesis.Pigment Cell & Melanoma Research 10/2010; 24(2):309-25. · 5.06 Impact Factor -
Article: Dacarbazine treatment before peptide vaccination enlarges T-cell repertoire diversity of melan-a-specific, tumor-reactive CTL in melanoma patients.
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ABSTRACT: Combination of chemotherapy and immunotherapy to increase the effectiveness of an antitumor immune response is currently regarded as an attractive antitumor strategy. In a pilot clinical trial, we have recently documented an increase of melanoma antigen A (Melan-A)-specific, tumor-reactive, long-lasting effector-memory CD8(+) T cells after the administration of dacarbazine (DTIC) 1 day before peptide vaccination in melanoma patients. Global transcriptional analysis revealed a DTIC-induced activation of genes involved in the immune response and leukocyte activation. To identify the possible mechanisms underlying this improved immune response, we have compared the endogenous and the treatment-induced anti-Melan-A response at the clonal level in patients treated with the vaccine alone or with DTIC plus vaccine. We report a progressive widening of T-cell receptor (TCR) repertoire diversity, accompanied by high avidity and tumor reactivity, only in Melan-A-specific T-cell clones of patients treated with chemoimmunotherapy, with a trend toward longer survival. Differently, patients treated with vaccine alone showed a tendency to narrowing the TCR repertoire diversity, accompanied by a decrease of tumor lytic activity in one patient. Collectively, our findings indicate that DTIC plus vaccination shapes the TCR repertoire in terms of diversity and antitumor response, suggesting that this combined therapy could be effective in preventing melanoma relapse.Cancer Research 09/2010; 70(18):7084-92. · 7.86 Impact Factor -
Article: How to diagnose nonpigmented skin tumors: a review of vascular structures seen with dermoscopy: part I. Melanocytic skin tumors.
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ABSTRACT: Dermoscopy is a noninvasive tool that can be helpful in the diagnosis of nonpigmented skin tumors. This is because dermoscopy permits the visualization of key vascular structures that are usually not visible to the naked eye. Much work has concentrated on the identification of specific morphologic types of vessels that allow a classification into melanocytic versus nonmelanocytic and benign versus malignant nonpigmented skin tumors. Among a broad spectrum of different types of vascular patterns, six main morphologies can be identified. These are comma-like, dotted, linear-irregular, hairpin, glomerular, and arborizing vessels. With some exceptions, comma, dotted, and linear irregular vessels are associated with melanocytic tumors, while the latter three vascular types are generally indicative of keratinocytic tumors. Aside from vascular morphology, the architectural arrangement of vessels within the tumor and the presence of additional dermoscopic clues are equally important for the diagnosis. This article provides a general overview of the dermoscopic evaluation of nonpigmented skin tumors and is divided into two parts. Part I discusses the dermoscopic vascular patterns of benign and malignant melanocytic skin tumors. Part II discusses the dermoscopic vascular patterns of benign and malignant nonmelanocytic nonpigmented skin tumors. In each part, additional special management guidelines for melanocytic and nonmelanocytic nonpigmented skin tumors, respectively, will be discussed.Journal of the American Academy of Dermatology 09/2010; 63(3):361-74; quiz 375-6. · 3.99 Impact Factor -
Article: How to diagnose nonpigmented skin tumors: a review of vascular structures seen with dermoscopy: part II. Nonmelanocytic skin tumors.
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ABSTRACT: Nonmelanoma skin cancer refers to a broad class of tumors, including actinic keratosis, basal cell carcinoma, and squamous cell carcinoma, and as a group these are the most frequent cancers occurring in light skinned humans. In contrast to the rarity of amelanotic melanoma, nonmelanoma skin cancer commonly lacks pigmentation. Although these tumors rarely cause death related to metastases, they commonly destroy underlying tissues and should be removed at the earliest possible stage. Dermoscopy improves the clinical diagnosis of nonpigmented skin tumors by allowing the visualization of specific vascular structures that are usually not visible to the naked eye. Dermoscopic vascular patterns of several nonmelanocytic nonpigmented skin tumors, such as sebaceous hyperplasia, seborrheic keratosis, clear cell acanthoma, Bowen disease, or nodular cystic basal cell carcinoma are highly specific, allowing a ready diagnosis in most cases. Others, such as actinic keratosis, pyogenic granuloma, or uncommon adnexal tumors, may be difficult to differentiate even with the aid of dermoscopy. For this reason, general guidelines have been established to assist in making the most appropriate management decision. In the second part of this review of dermoscopic vascular structures of nonpigmented skin tumors, the dermoscopic patterns associated with benign and malignant nonmelanocytic skin tumors and recommendations for the management of these tumors will be discussed.Journal of the American Academy of Dermatology 09/2010; 63(3):377-86; quiz 387-8. · 3.99 Impact Factor
Top co-authors
Top Journals
Institutions
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2011
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Klinički centar Niš
Niš, Serbia -
Sapienza University of Rome
- Department of Molecular Medicine
Roma, Latium, Italy
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2010–2011
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Medical University of Graz
Graz, Styria, Austria -
IRCCS Ospedale Casa Sollievo della Sofferenza
- Dermatology
San Giovanni Rotondo, Apulia, Italy
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2006–2010
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Istituto Dermatologico San Gallicano - Istituti Fisioterapici Ospitalieri
Roma, Latium, Italy
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2009
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Istituto Regina Elena - Istituti Fisioterapici Ospitalieri
Roma, Latium, Italy
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