Divergence between the high rate of p53 mutations in skin carcinomas and the low prevalence of anti-p53 antibodies

Circulating anti-p53 antibodies have been described and used as tumoural markers in patients with various cancers and strongly correlate with the p53 mutated status of the tumours. No study has yet looked at the prevalence of such antibodies in skin carcinoma patients although these tumours have been shown to be frequently p53 mutated. Most skin carcinoma can be diagnosed by examination or biopsy, but aggressive, recurrent and/or non-surgical cases' follow up would be helped by a biological marker of residual disease. We performed a prospective study looking at the prevalence of anti-p53 antibodies using an ELISA technique in a series of 105 skin carcinoma patients in comparison with a sex- and age-matched control skin carcinoma-free group (n = 130). Additionally, p53 accumulation was studied by immunohistochemistry to confirm p53 protein altered expression in a sample of tumours. Anti-p53 antibodies were detected in 2.9% of the cases, with a higher prevalence in patients suffering from the more aggressive squamous cell type (SCC) of skin carcinoma (8%) than for the more common and slowly growing basal cell carcinoma type or BCC (1.5%). p53 protein stabilization could be confirmed in 80% of tumours studied by IHC. This low level of anti-p53 antibody detection contrasts with the high rate of p53 mutations reported in these tumours. This observation shows that the anti-p53 humoral response is a complex and tissue-specific mechanism. © 2001 Cancer Research Campaign http://www.bjcancer.co

Aflatoxin biosynthetic pathway extrolites in airborne Aspergilli series Versicolores

International audienceThe Aspergilli of the series Versicolores include several airborne species to which we are exposed daily. Most of them synthesise sterigmatocystin, a mycotoxin precursor of aflatoxins recognised as potentially carcinogenic for humans (group 2B) by the International Agency for Research on Cancer. Our objective was to study the potential role of these moulds in the synthesis of extrolites of the aflatoxin biosynthetic pathway. A total of 124 isolates belonging to the eight species of the series Versicolores collected in French bioaerosols were studied: Aspergillus amoenus (n=1), Aspergillus creber (n=45), Aspergillus fructus (n=2), Aspergillus jensenii (n=39), Aspergillus protuberus (n=6), Aspergillus puulaauensis (n=5), Aspergillus sydowii (n=14) and Aspergillus tabacinus (n=2). All these isolates and a reference strain of each species were extracted using ethyl acetate acidified with 1% (v/v) acetic acid. In each extract, we screened for the following extrolites of the aflatoxin biosynthetic pathway by UPLC-HRMS: norsolorinic acid, versicolorin A, 6-demethylsterigmatocystin, sterigmatocystin, 8-O-methylsterigmatocystin, 5-methoxysterigmatocystin and aflatoxins B 1 , B 2 , G 1 and G 2 . All extrolites, except aflatoxins, were found variably among species. Sterigmatocystin was found in extracts of all eight Versicolores species, including A. sydowii and A. tabacinus whose ability to synthesise sterigmatocystin was questioned or unknown, respectively

Modalités pratiques de traitement des kératoses actiniques par photothérapie dynamique topique en lumière du jour avec l’aminolévulinate de méthyle

International audienceActinic keratosis (AK), also known as solar keratosis or pre-cancerous keratosis, is frequently observed in areas of skin exposed to sunlight, particularly in light-skinned patients. In France, photodynamic therapy using red light (conventional PDT) and methylamino 5-levulinate (MAL) is indicated in the treatment of thin or non-hyperkeratotic and non-pigmented multiple AK lesions or large zones covered with AK lesions. It is well-known for its efficacy but also for its side effects, especially pain during illumination, which can limit its use. An alternative to PDT using natural daylight has recently been proposed to treat actinic keratosis lesions, and results in greater flexibility as well as significant reduction in pain. The lesions are prepared as for conventional PDT, with MAL cream being applied by the physician or the patient, after which they are exposed to natural daylight for 2hours. The lesions are then gently cleansed and protected from natural light for 24hours. This paper seeks to provide a precise description of the daylight PDT procedure for the treatment of AK

Assessment of quality of life using Skindex-16 in patients with advanced basal cell carcinoma treated with vismodegib in the STEVIE study

Health-related quality of life (HRQoL) data are limited in patients with advanced basal cell carcinoma. To report HRQoL outcomes based on STEVIE (NCT01367665), a phase 2 study of vismodegib safety in patients with metastatic BCC or locally advanced BCC that is unsuitable for surgery or radiotherapy. Skindex-16 and MD Anderson Symptom Inventory (MDASI) questionnaires were completed at baseline and at three subsequent visits. Clinically meaningful improvement was defined as a ≥10-point decrease from baseline (Skindex-16) or improvement of at least 3 points from baseline (MDASI). HRQoL-evaluable patients with locally advanced BCC (n = 730) had ≥10-point improvements in Skindex-16 emotion domain scores at all time points. Changes in symptom and function scores in these patients or in any domain scores at any time point in patients with metastatic BCC (n = 10) were not clinically meaningful. Of 10 patients with symptomatic metastatic BCC at baseline, six had ≥3-point improvements in MDASI symptom severity. Skindex-16 and MDASI showed improvement in HRQoL in vismodegib-treated patients with locally advanced or metastatic BCC or BCC

Vismodegib in patients with advanced basal cell carcinoma: Primary analysis of STEVIE, an international, open-label trial

International audienceBACKGROUND: The SafeTy Events in VIsmodEgib study (STEVIE, ClinicalTrials.gov, NCT01367665), assessed safety and efficacy of vismodegib-a first-in-class Hedgehog pathway inhibitor demonstrating clinical benefit in advanced basal cell carcinoma (BCC)-in a patient population representative of clinical practice. Primary analysis data are presented.PATIENTS AND METHODS: Patients with locally advanced or metastatic BCC received oral vismodegib 150~mg/d until progressive disease, unacceptable toxicity, or withdrawal. Primary objective was safety. Efficacy variables were assessed as secondary end-points.RESULTS: Evaluable adult patients (N~=~1215, 1119 locally advanced; 96 metastatic BCC) from 36 countries were treated; 147 patients (12%) remained on study at time of reporting. Median (range) treatment duration was 8.6 (0-44) months. Most patients (98%) had >=1 treatment-emergent adverse event (TEAE). The incidence of the most common TEAEs was consistent with reports in previous analyses. No association between creatine phosphokinase (CPK) abnormalities and muscle spasm was observed. Serious TEAEs occurred in 289 patients (23.8%). Exposure >=12 months did not lead to increased incidence or severity of new TEAEs. The majority of the most common TEAEs ongoing at time of treatment discontinuation resolved by 12 months afterwards, regardless of Gorlin syndrome status. Response rates (investigator-assessed) in patients with histologically confirmed measurable baseline disease were 68.5% (95% confidence interval (CI) 65.7-71.3) in patients with locally advanced BCC and 36.9% (95% CI 26.6-48.1) in patients with metastatic BCC.CONCLUSIONS: The primary analysis of STEVIE demonstrates that vismodegib is tolerable in typical patients in clinical practice; safety profile is consistent with that in previous reports. Long-term exposure was not associated with worsening severity/frequency of TEAEs. Investigator-assessed response rates showed high rate of tumour control. CLINICALTRIALS.GOV: NCT01367665