Characteristics of Familial Melanoma in Valencia, Spain, Based on the Presence of CDKN2A Mutations and MC1R Variants.

Melanoma results from a complex interplay between environmental factors and individual genetic susceptibility. Familial melanoma is attributable to predisposition genes with variable penetrance. The aim of this study was to identify differences between familial melanoma and sporadic cases in our population, based on the presence of CDKN2A mutations and MC1R variants. Comparing 107 patients with familial melanoma from 87 families (17% CDKN2A mutated) with 1,390 cases of sporadic melanomas, the former were younger and exhibited an increased prevalence of atypical naevi and squamous cell carcinoma (SCC). CDKN2A mutation carriers presented more atypical naevi, multiple melanomas, and basal cell carcinoma, while non-carriers were more likely to have light-coloured hair, atypical naevi, and SCC. MC1R variants decreased the age at diagnosis in all groups and were associated with an increased prevalence of SCC, especially in patients with familial melanoma without CDKN2A mutations. These characteristics may help to establish prevention measures targeting patients with familial melanoma in the Mediterranean area.

Efficacy of etanercept in psoriatic patients previously treated with infliximab.

BACKGROUND: There are few data to enable us to ascertain whether switching to another systemic agent is useful in patients with psoriasis who have not responded favorably to a first systemic treatment. OBJECTIVE: To evaluate the efficacy and safety of etanercept in patients with moderate-to-severe plaque psoriasis previously treated with infliximab. METHODS: We analyzed data from patients with moderate-to-severe psoriasis and a poor primary or secondary response to infliximab, and who were later treated with etanercept. RESULTS: Data were collected from 8 patients who were first treated with infliximab. At 54 weeks of therapy, 25% had a psoriasis area and severity index (PASI) of 75. At 24 weeks of therapy with etanercept, 75% had a PASI of 75. Consecutive administration of both therapies did not increase the number of adverse events. LIMITATIONS: The data should be regarded with caution due to the scant number of patients. CONCLUSIONS: Switching from infliximab to etanercept can be useful and safe in nonresponders.

Prognostic factors in localized invasive cutaneous melanoma: high value of mitotic rate, vascular invasion and microscopic satellitosis.

The aim of this study was to determine independent clinical and pathological prognostic factors for overall and disease-free survival in Spanish melanoma patients. Eight hundred and twenty-three patients with localized melanoma and complete clinical and pathological information were evaluated. The age at diagnosis, gender, location, tumour thickness, invasion level, ulceration, histological subtype, inflammatory infiltrate, mitotic rate, vascular invasion, microscopic satellitosis, regression and cell type were all included. Univariate and multivariate Cox regression analyses were performed for overall and disease-free survival. Gender, histological subtype, tumour thickness, invasion level, ulceration, inflammatory infiltrate, microscopic satellitosis, vascular invasion and mitotic rate were related to overall and disease-free survival in univariate analysis. Age and location were only related to disease-free survival. Only tumour thickness, vascular invasion and gender exhibited independent significance for overall survival in multivariate analysis. For disease-free survival, tumour thickness, location, mitotic rate, vascular invasion and microscopic satellitosis were the sole independent factors. It can be concluded that the Breslow thickness remains the most significant prognostic factor for the survival of patients with localized cutaneous melanoma. Our results support the inclusion of microscopic satellitosis and vascular invasion in the current American Joint Committee on Cancer (AJCC) staging system, although further studies evaluating their separate influence are needed. Mitotic rate is confirmed as an objective and independent predictor of disease-free survival for melanoma patients that should be considered in further revisions of the mentioned staging system.

Survival advantage of women in localized melanoma mainly relies on clinical-pathological differences by sex. A retrospective study of 1,607 patients in Valencia, Spain.

BACKGROUND: Among melanoma patients, women have a better prognosis than men but the differences might be due to a different presentation of melanoma. OBJECTIVES: The aim of this study was to identify differences in clinical presentation and survival in cutaneous melanoma between men and women in a Spanish population stratified by age. MATERIALS & METHODS: In total, 1,607 consecutive patients with localized cutaneous melanoma and complete clinical and pathological information were evaluated. Average follow-up was 5 years. Patients were stratified by age into three groups: ≤ 45 years, 46-60 years, and >60 years. Disease-free survival, overall-survival and disease-specific survival were generated using the Kaplan-Meier method. Multivariate survival analyses were evaluated using Cox modelling. RESULTS: Melanoma presented more frequently in the trunk in male patients and in the lower extremities and acral location in female patients. Men presented thicker tumors than women. However, for histological type, mitotic rate and ulceration there were no significant differences between the sexes. In the univariate survival analyses, women showed better disease-free, overall and disease-specific survival in the younger age group, compared with males of the same group. After adjusting for anatomical site, Breslow thickness, mitotic rate and presence of ulceration, there were no differences between males and females in any of the three age groups. CONCLUSION: The superior survival for women over men did not persist after adjusting for multiple prognostic variables such as anatomical site, Breslow thickness, mitotic rate and ulceration.

[Renal involvement in the human immunodeficiency virus infection]. / Alteración renal en la infección por el virus de la inmunodeficiencia humana.

BACKGROUND AND OBJECTIVE: Although renal pathologies are becoming an emergent problem in the population infected by the human immunodeficiency virus (HIV), there is very scarce information about the natural course of this problem. The objective of the present study is to describe renal lesions in an autopsy series of HIV-infected patients never treated with antiretroviral therapies. PATIENTS AND METHOD: Autopsy information has been retrospectively retrieved from 61 HIV-infected subjects (mean age, 36,9 [8,4] years; 58,6% drug abusers, 84% males) died in our hospital between 1984 and 1997. None of the patients received antiretroviral therapy. All autopsy and clinical reports were considered, as well as basic analytical parameters about renal function. Renal autopsy samples were specifically reviewed. RESULTS: At the time of the last admission, 9.8% of patients had renal insufficiency, who made up 44.3% of patients having renal insufficiency anytime. Infections were the main cause of death (76%). The majority of patients (93.4%) showed histopathological renal abnormalities, which were highly heterogeneous. Renal lesions were mainly located on the tubules (96.7%) and the interstitium (60.7%). Moreover, glomeruli were affected in 55.7% of patients. Most frequent histopathological diagnosis was acute tubular necrosis (16.4%) and septic nephritic abscesses (16.4%), followed by tubulointerstitial nephritis (9%). HIV-associated nephropathy was present in two patients (3.3%). There were no significant differences when considering the existent of renal failure. CONCLUSIONS: Renal histological abnormalities are frequent in the natural evolution of HIV infection. There is an important heterogeneity of lesions, mainly involving tubules, interstitium and mesangium. The cause of renal lesions is predominantly septic, according to the chief systemic process. It does not exist any relationship between renal analytical parameters and the presence of renal damage.

Influence of loss of function MC1R variants in genetic susceptibility of familial melanoma in Spain.

We explored the presence of germline alterations in CDK4 exon 2, CDKN2A and MC1R in a hospital-based study of 89 melanoma cases from 89 families with at least two members affected by cutaneous melanoma. A total of 30% of the melanoma kindreds studied were carriers of CDKN2A variants, and three of these variants were known predominant alleles that have been identified earlier in Mediterranean populations (p.G101W, p.V59G and c.358delG). We observed a higher frequency of nonsynonymous MC1R variants in these Spanish melanoma kindreds (72%) with respect to the general population (60%). We observed a higher frequency of nonsynonymous MC1R variants in this Spanish melanoma kindred (72%) respect to general population (60%). A new classification of MC1R variants based on their functional effects over melanocortin-1 receptor, including the dominant-negative effect of some of them in heterozygotes, suggested an association of loss of function MC1R variants and multiple primary melanoma cases from melanoma kindred (odds ratio: 6.07, 95% confidence interval: 1.35-27.20). This study proposes the relevance of loss of function MC1R variants in the risk of melanoma in multiple primary melanoma cases with family history from areas with low melanoma incidence rate.

Clinicopathological analysis of 1571 cutaneous malignant melanomas in Valencia, Spain: factors related to tumour thickness.

Epidemiological studies on cutaneous melanoma in Mediterranean countries are scarce. Our aim was to perform a descriptive analysis of melanoma cases diagnosed in Valencia, Spain, and to evaluate the relationship between Breslow thickness and some clinical features. A total of 1571 patients with histologically confirmed cutaneous malignant melanoma diagnosed at the two main referral melanoma centres were evaluated retrospectively. For each patient the following clinical and pathological characteristics were selected: age, gender, anatomic site, histogenetic type, Breslow thickness, presence of ulceration, the stage, and symptoms such as bleeding, changes in size and colour, altered sensations and previous traumas. Chi-squared tests were performed together with logistic regression to evaluate the relationship of variables with tumour thickness. Tumour thickness was independently correlated with increasing age, presence of bleeding, location on hand or foot, and presence of altered sensations. Female sex and presence of a change in colour were associated with thin melanomas. Ideally, public awareness campaigns concerning the risks that exist should be aimed at subgroups such as men and people of an advanced age who generally present with thicker tumours. Emphasis should be placed on irregularities or changes in pigmentation, as these appear to be the first indicators of the development of a melanoma.