Giuseppe Ricotti

Immunohistochemical study of apoptosis markers and involvement of chemokine CXCR4 in skin Merkel cell carcinoma

Background  Merkel cell carcinoma (MCC) is a rare, aggressive cancer of the skin that mainly affects elderly patients. Because of its rarity, there is no established treatment or proven markers to guide therapy or prognosis. Immunohistochemical expression of apoptosis proteins is considered a useful marker of both malignancy and tumour progression. Apoptosis plays a fundamental role in skin homeostasis, and apoptotic cells have been detected in normal and diseased skin. Chemokines posses a wide range of biological activities and CXCR4 is expressed in some cancer cells, where it plays an efficient role in metastasis formation.

Color-Based Method for Fractal Dimension Estimation of Pigmented Skin Lesion Contour

Early diagnosis in the analysis of suspected pigmented skin lesions is very important in order to excise precociously malignant lesions and to avoid unnecessary removal of the benign ones. Decisions are based on colors, shapes and irregularities of the lesions and the differences of these characteristics in repeated observations. An objective measure of the boundary irregularity can be obtained estimating fractal dimension, DF, of the lesion contour. Since previous attempts have given contradictory results, we propose a method based on chromatic image characteristics, instead of the more common black and white. The image acquisition was performed by means of a high resolution apparatus, the SkinLab system and fractal dimension of processed image contour has been estimated by the box-counting method implementing the algorithm on Matlab software. The method could help in discriminating between nevi and melanomas and in following lesion evolution with time.

Results of a prospective phase II trial with oral low-dose bexarotene plus photochemotherapy (PUVA) in refractory and/or relapsed patients with mycosis fungoides

IntroductionBexarotene is a synthetic retinoid effective in early and advanced stages of mycosis fungoides (MF)/Sezary Syndrome (SS) both in monotherapy and combination schemes.ObjectivesWe aimed to assess disease response to low-dose bexarotene and PUVA in maintenance in refractory and/or resistant patients with early and advanced stage MF/SS.MethodsWe followed prospectively 21 patients (stages IB-IV): 15 with early stage MF and 6 with advanced disease. “Mini” and standard protocols were respectively applied to patients who failed PUVA or several systemic regimens. The dose of bexarotene and the administration of PUVA were titrated individually and tailored during induction and maintenance according to previous therapy, disease stage and toxicity. We evaluated overall response (OR) at the end of maintenance, safety and event-free survival (EFS).ResultsAfter induction phase, OR was 85.6%, higher in early MF (93.4%) than in advanced disease (66.6%). At the end of maintenance, OR was 76.2%, including 33.3% of CR. Median EFS for the whole group was 31 months. Bexarotene was well tolerated regarding the side effects, with prophylaxis and progressive drug increase in the induction phase of the protocol. Side effects were mainly of low and moderate grades.ConclusionsWe observed a favorable rate of therapeutic effects and few, generally mild, side effects with low doses of bexarotene combined with PUVA.

Cdc42 is involved in basal cell carcinoma carcinogenesis

Abstract Basal cell carcinoma (BCC) is the most common type of skin cancer in older persons and is a rapidly rising incidence. E-cadherin-mediated cell–cell adhesion activates Cdc42, a Rho GTPase essential for cell polarity in numerous settings. No study has yet addressed a biological significance of Cdc42 alterations in BCC pathogenesis. Our aim was to investigate E-cadherin-dependent cell–cell contacts and Cdc42 activity in BCC formation. We evaluated E-cadherin and Cdc42 expression by immunohistochemistry and Western blot analysis in samples of 15 normal skin (NS) and 30 BCC (10 superficial, 9 nodular and 11 infiltrative subtypes). Low E-cadherin and high Cdc42 immunohistochemical expression were found in BCC samples compared with NS. E-cadherin staining was significantly reduced in infiltrative BCC compared with superficial and nodular. A significantly greater Cdc42 expression was observed in BCC compared with NS; moreover, superficial BCC had a significantly lower Cdc42 expression in respect to the other subtypes. Western blot analysis confirmed the significantly decreased E-cadherin expression in infiltrative BCC as well as Cdc42 reduction in superficial BCC in respect to the other subtypes. In BCC the increased Cdc42 in association with reduced E-cadherin might contribute to the disruption of adhesion mechanisms and to the loss of cell polarity, thus explaining a mechanism by which cancer cells can escape from the control of adjacent normal keratinocytes. Our study also showed that Cdc42 and E-cadherin expression differed according to aggressive behaviour of BCC subtypes and suggested important functions of these molecules in regulating tumour demarcation and progression.

Isolated limb infusion chemotherapy with or without hemofiltration for recurrent limb melanoma

AIM To better define the efficacy and the safety of intra-arterial infusion performed with or without hemofiltration for recurrent limb melanoma. METHODS Patients with the following characteristics were included in the study: recurrent limb melanoma not indicated for surgical resection, measurable disease in the extremity, > 18 years, performances status (Eastern Cooperative Oncology Group ) was 0-1 and life expectancy of at least 6 mo. Twenty nine consecutive patients were enrolled in the study. Patients underwent fluoroscopic placement of angiographic arterial and venous catheters to infuse the drug in the artery [isolated limb infusion (ILI)], and to stop the out flow (venous). Melphalan was rapidly infused into the isolated limb via the arterial catheter after the inflation of venous balloon catheter. Then the circulation of the limb was completely blocked with a pneumatic cuff at the root of the limb. Haemofiltration (HF) was available only in the main center, and was performed with an extracorporeal perfusion system, in order to reduce high systemic toxic peaks of drug. RESULTS Thirty seven ILI were done in 29 cases (31 ILI-HF and 6 ILI) between 2001 and 2014 at Ancona and Pesaro Hospitals, Italy. Clinical outcomes were monitored 30 d after treatment. Eleven patients (38%) received infusion of melphalan alone, 7 (24%) melphalan associated to mitomicin C and 7 (24%) melphalan associated to cisplatin, the remaining 4 were treated with cisplatin, melphalan and epirubicin or cisplatin and mitomicin C. The overall response rate was 66%, in particular, 3 patients (10%) were complete responders and 16 (56%) were partial responders; whereas 7 patients (24%) had stable disease, and 3 (10%) showed progressive disease. Limb toxicity was assessed adopting Wieberdink scale, with evidence of 90% of low grade (I and II) toxicity. CONCLUSION ILI-HF and ILI are effective and safe treatments for recurrent non-resectable limb melanoma. They present evidence of favorable clinical benefit and is effective in delaying progression.

Gender differences and outcome of melanoma patients.

Background In the United States, 80,000 cases of melanoma are expected in 2014, representing 5% and 4% of all diagnosis of cancer in men and women, respectively. In Italy in 2013, there were an estimated 10,500 cases of cutaneous melanoma, with an incidence of 14.3 cases per 100,000 male population and 13.6 cases per 100,000 female population. Female melanoma patients generally exhibit significantly longer survival than male patients. The aim of this study is to evaluate the role of gender in survival of melanoma patients and the relationship between gender and pathologic features of the neoplasm.