Arianna Corbu

The predictive value of CD8, CD4, CD68, and human leukocyte antigen-D-related cells in the prognosis of cutaneous malignant melanoma with vertical growth phase.

To establish the prognostic value of immune system cells that infiltrate melanoma, the authors evaluated the distribution and density of T lymphocyte subsets, macrophages, and dendritic cells in samples of primary cutaneous melanoma from 47 patients with Stage I and II melanoma according to the American Joint Committee on Cancer staging system.

Satellite cell characterization from aging human muscle

Abstract Objectives: Satellite cells (SCs) are skeletal muscle progenitor cells located between the basal lamina and the sarcolemma of muscle fibers. They are responsible for muscle growth and repair. In humans, aging results in the depletion of the SC population and in its proliferative activity, but not in its function. It has not yet been determined whether under conditions of massive muscle fiber death in vivo, the regenerative potential of SCs is totally or partially compromised in old muscle. No studies have yet tested whether advanced age is a factor that restrains the response of SCs to muscle denervation in humans; this is also due to difficulties in the isolation and in the culture of SCs from a small human surgery fragment. The aim of this study was to study in depth muscle regeneration analysing the SC ability of SCs to proliferate and differentiate in aging human patients. Methods: In order to study in more detail the molecular mechanism, the proliferative and differentiative ability of aging SCs, we isolated SCs from aging human muscle biopsies and analysed their morphology by transmission electron microscopy and immunocytochemical analysis (antibodies against desmin, N-CAM and M-cadherin) and their capacity to grow and to expand in vitro. Moreover, in order to evaluate gene expression of myogenic regulatory factors Myf5, MyoD and myogenin (Myf4), RT-PCR was performed. Results and discussion: SCs isolated from aging human muscle biopsies and plated into favorable proliferation and differentiation conditions were able to proceed through the myogenic program and actively form myotubes, although taking longer than the young control sample. The RT-PCR analysis together with the ultrastructural SC features showed that the myogenic potential seemed to be compromised during the aging human muscle proliferation in vitro.

Expression of survivin protein in pterygium and relationship with oxidative DNA damage

Ultraviolet radiation is known to cause oxidative DNA damage and is thought to be a major factor implicated in the pathogenesis of pterygium. Among all the photo‐oxidative DNA products, the 8‐hydroxydeoxyguanosine (8‐OHdG) is regarded a sensitive and stable biomarker for evaluating the degree of DNA damage. The protein p53 is a major cell stress regulator that acts to integrate signals from a wide range of cellular stresses. UV radiation has a carcinogenic effect resulting in DNA damaged cells with loss of normal growth control. This assumption is supported by the association between UV‐B exposure and activation of survivin, a member of the inhibitor of apoptosis protein family (IAP), highly up‐regulated in almost all types of human malignancy. In this study we demonstrate, for the first time in pterygium, the immunohistochemical presence of survivin, and investigate the correlation between survivin, p53 and 8‐OHdG. Our results demonstrate that oxidative stress could lead to a significant activation of survivin expression, suggesting that this might be an important event in the development of pterygium, inducing and supporting a hyperproliferative condition. Survivin expression in pterygium would counteract UV‐B‐induced apoptosis and would cooperate with loss of p53. The co‐operation between survivin and functional loss of p53 might provide a general mechanism for aberrant inhibition of apoptosis that could be responsible for the development of pterygium and its possible progression to neoplasia.

Finding of conjunctival melanocytic pigmented lesions within pterygium

Aims : Conjunctival pigmented lesions have characteristic clinical and histopathological appearances. Melanocytic pigmented lesions commonly occur in the conjunctiva, although they have not been previously reported in pterygium, a common lesion which originates from conjunctiva. Our aim was to evaluate the possibility of an association between pterygium and conjunctival melanocytic pigmented lesions.

Prognostic prediction of the immunohistochemical expression of p16 and p53 in cutaneous melanoma : a comparison of two populations from different geographical regions

p16INK4a and p53 are tumor-suppressor genes frequently altered in various malignancies, including cutaneous melanoma. The purpose of the study was to establish the prognostic value of immunohistochemical expression of p16INK4a a and p53 in sporadic cutaneous melanoma (CM) in two regions with a high-risk for melanoma in Italy and Ecuador. Immunohistochemical staining of p16 and p53 was performed in samples of primary CM from 82 patients with Stage I and II melanoma according to the American Joint Committee on Cancer (AJCC) staging system. Survival differences between categories of p16 or p53 expression were analyzed using the product-limit procedure (Kaplan-Meier method, log-rank test). Clinical variables (gender, age, tumor location, Clarks level, thickness) were correlated with survival and p16 or p53 expression. p16 nuclear immunoreactivity was observed in 85% of Italian patients compared to 48.7% of Ecuadorians; a small number of cases showed p53 immunoreactivity in both populations. Only nuclear p16 expression exhibited a significant correlation with survival (Italians p=0.001, Ecuadorians p=0.017) but did not appear to correlate with any clinicopathological parameter. No significant difference was observed in survival with regard to p53 expression or cytoplasmic p16. Our results demonstrate that nuclear expression of p16 can be considered a molecular prognostic factor in patients with sporadic CM and indicate its importance as a clinical marker.