Whereas accepted models of tumorigenesis exist for genetic lesions, the timing of epigenetic alterations in cancer is not clearly understood. We have analyzed the profile of aberrations in DNA methylation occurring in cells lines and primary tumors of one of the best-characterized mouse carcinogenesis systems, the multistage skin cancer progression model. Initial analysis using high-performance capillary electrophoresis and immunolocalization revealed a loss of genomic 5-methylcytosine associated with the degree of tumor aggressiveness. Paradoxically, this occurs in the context of a growing number of hypermethylated CpG islands of tumor suppressor genes at the most malignant stages of carcinogenesis. We have observed this last phenomenon using two approaches, a candidate gene approach, studying genes with well-known methylation-associated silencing in human tumors, and a mouse cDNA microarray expression analysis after treatment with DNA demethylating drugs. The transition from epithelial to spindle cell morphology is particularly associated with major epigenetic alterations, such as E-cadherin methylation, demethylation of the Snail promoter, and a decrease of the global DNA methylation. Analysis of data obtained from the cDNA microarray strategy led to the identification of new genes that undergo methylation-associated silencing and have growth-inhibitory effects, such as the insulin-like growth factor binding protein-3. Most importantly, all of the above genes were also hypermethylated in human cancer cell lines and primary tumors, underlining the value of the mouse skin carcinogenesis model for the study of aberrant DNA methylation events in cancer cells.

Terra firma-forme dermatosis is characterized by 'dirty' brown-grey cutaneous patches and plaques that can simply be eradicated by forceful swabbing with alcohol pads. The pathogenesis has been attributed to abnormal and delayed keratinization. Although affected patients present with typical lesions, the disorder is not well-known by dermatologists. In this report, we describe two patients with terra firma-forme dermatosis in the setting of xerosis cutis and atopic dermatitis. From a clinical point of view, we lay emphasis on its unique expression and diagnosis/treatment. From a histological perspective, we highlight its resemblance to dermatosis neglecta and speculate on the role of 'neglect' in a patient with seemingly adequate hygiene. The role of urea containing emollients in the development of this disorder remains to be determined.

Latex allergy is an IgE-mediated immediate hypersensitivity response to natural rubber latex (NRL) protein with a variety of clinical signs ranging from contact urticaria, angioedema, asthma, and anaphylaxis. Major allergens include dipped latex products such as gloves and balloons. In highest risk for NRL allergy are patients with spina bifida, but health care workers and others who wear latex gloves are also at risk. NRL allergic patients may also react to fruits/foods, especially banana, kiwi, and avocado. Diagnosis is made by a positive latex RAST and/or skin prick test or challenge test to NRL. Allergen avoidance and substitution and the use of latex-safe devices including synthetic gloves (vinyl, synthetic polyisoprene, neoprene, nitrile, block polymers, or polyurethane) are essential for the affected patient. Accommodation in the workplace may include the use of powder-free, low-allergen NRL gloves or synthetic gloves. These preventive measures have significantly reduced the prevalence of reported reactions to NRL. Hyposensitization is not yet feasible.

No abstract

Human papillomavirus (HPV) is the most common sexually transmitted disorder in young, sexually active populations in the USA and Europe. Giant condyloma acuminatum (GCA) is a unique variant of condyloma acuminata, characterized by local aggressive behaviour despite benign histology. It carries a substantial risk of squamous cell carcinoma. Various treatments have been used, but response is often poor and recurrence rates high. We present a case of GCA successfully treated with a combination of surgical excision, oral acitretin and topical imiquimod. The diagnosis was based on histological examination, immunohistochemical analysis and in situ hybridization for HPV 6 and 11. We recommend a trial of oral retinoid and topical imiquimod in selected cases of GCA.

No abstract

These findings indicate a discordant expression of bcl-2 and bax/bcl-x in psoriatic epidermis. Increased bcl-x expression might contribute to the antiapoptotic response in psoriatic keratinocytes. The presence of strong bax expression with a concomitant decrease in bcl-2 expression suggests either a functional defect in bax protein or an inherent/acquired resistance to bax-mediated apoptosis in psoriatic keratinocytes.

Hepatitis C virus (HCV) is the main cause of parenterally transmitted non-A, non-B viral hepatitis. In recent years, a significant association between lichen planus and chronic HCV infection has been reported. Anti-HCV antibody status was evaluated by ELISA in 54 patients with lichen planus and 54 patients with minor dermatological disorders. PCR was used to examine HCV RNA from serum and lesional and nonlesional cutaneous biopsy samples of HCV-infected patients. Seven patients with lichen planus (12.9%) and two patients in the control group (3.7%) were anti-HCV antibody positive. Five out of seven patients with anti-HCV antibodies had demonstrable HCV RNA in lesional skin biopsies. The viral RNA was absent in three out of four patients with lichen planus whose serum samples were positive for HCV RNA and agreed to biopsy of nonlesional skin. The prevalence of HCV infection is not increased in Turkish patients with lichen planus. However our findings suggest that the virus may play a potential pathogenic role by replicating in cutaneous tissue and triggering lichen planus in genetically susceptible HCV-infected patients.