PTCH promoter methylation at low level in sporadic basal cell carcinoma analysed by three different approaches

Please cite this paper as: PTCH promoter methylation at low level in sporadic basal cell carcinoma analysed by three different approaches. Experimental Dermatology 2010. Abstract: Basal cell carcinoma (BCC) is the most common form of skin cancer. Mutations of the PTCH hallmark gene are detected in about 50-60% of BCCs, which raises the question whether other mechanisms such as promoter methylation can inactivate PTCH. Therefore, we performed methylation analysis of the PTCH promoter in a total of 56 BCCs. The sensitivity of three different methods, including direct bisulphite sequencing PCR, MethyLight and high-resolution melting (HRM), was applied and compared. We found that HRM analysis of DNA from fresh tissue [rather than formalin-fixed and paraffin-embedded tissue (FFPE)] was the most sensitive method to detect methylation. Low-level methylation of the PTCH promoter was detected in five out of 16 analysed BCCs (31%) on DNA from fresh tissue but only in two (13%) samples on short-time stored FFPE DNA from the very same tumors. In contrast, we were unable to detect methylation by HRM on long-time stored DNA in any of the remaining 40 BCC samples. Our data suggest that (i) HRM on DNA extracted from fresh tissue is the most sensitive method to detect methylation and (ii) methylation of the PTCH promoter may only play a minor role in BCC carcinogenesis.

Facial basal cell carcinomas recurring after photodynamic therapy: a retrospective analysis of histological subtypes

Photodynamic therapy (PDT) is an established treatment for basal cell carcinomas (BCCs). Although recurrences are sometime observed, their histological patterns have never been specifically studied or compared with the one of the initial tumor.

Staged surgical therapy of basal cell carcinoma of the head and neck region: an evaluation of 500 procedures

QUESTIONS UNDER STUDY / PRINCIPLES: The surgical therapy of basal cell carcinoma (BCC) is especially demanding in the facial area. This retrospective study was undertaken to evaluate the outcome of staged surgical therapy (SST) of BCC of the head and neck region performed on an interdisciplinary basis at our institution. METHODS: Patients treated for BCC in the head and neck area between 1/1/1997 and 31/12/2001 were included in the study. The lesions were histologically evaluated. Diameter of lesion, number of stages, defect coverage, operation time, and recurrence and infection rates were analysed using descriptive and inferential statistical procedures. RESULTS: 281 patients were included in the study. SST was performed in two stages in 43.7%, in three stages in 12.9% and in four or more stages in 2.7%, depending on the type of tumour and the patient's pretreatment status. The total operating time per lesion averaged one hour. Defect coverage was achieved by direct closure (37.7%), by full thickness skin graft (39.5%), by split skin graft (1.1%), by local flaps (20.3%) or by composite grafts (1.1%). Median follow-up time was 58.5 months. Low rates of recurrence (3.6%) and infection (2%) were observed with this technique. CONCLUSIONS: The staged surgical therapy of basal cell carcinoma evaluated here offers a series of advantages in respect of patient comfort and safety and economy, while allowing precise histological safety with low infection rates and reliable long-term results.

Composite skin grafts for basal cell carcinoma defects of the nose

Basal cell carcinoma is the most frequent cutaneous cancer of the nose and is characterized by its local spreading and exceptionally rare tendency to metastasize. Since a significant advantage has been seen in surgery compared to other treatments, surgical excision ensuring the highest chance of cure is frequently employed. Excision defects of the nose may be covered with either local flap or a full-thickness skin graft. In resurfacing such defects following excision of basal cell carcinomas, we favor the technique of composite-skin grafting which involves the harvesting of composite-skin graft including the epidermis, dermis and superficial layers of subcutaneous tissue to obtain the required thickness in the recipient site. This technique was used for defects remaining after the excision of basal cell carcinomas in a series of 15 patients. The areas involved were lateral nasal region (5 cases), nasal tip (4 cases), dorsum (3 cases), alar lobule (2 cases), and soft triangle (1 case). The mean follow-up was 14.2 months. The color, texture and thickness of the composite-skin graft harvested from the preauricular site and the neck compare favorably with the skin of the nose region. Satisfactory results, both clinically and in patient appreciation, have been obtained in both the reconstruction site and the appearance of the donor site in all patients.

Dermatopathology in sub-Saharan Africa: a systematic 5-year analysis of all histopathological diagnoses from the Regional Dermatology Training Centre (RDTC) in Moshi, Tanzania.

BACKGROUND Proper diagnosis of skin diseases relies on dermatopathology, the most important diagnostic technique in dermatology. Unfortunately, there are few dermatopathology institutions in sub-Saharan Africa, where little is known about the spectrum of histopathological features observed. OBJECTIVES To investigate the spectrum of dermatopathological diagnoses made in a sub-Saharan African reference centre of a large, mainly rural area. PATIENTS/METHODS To retrospectively evaluate all dermatopathological diagnoses made over a period of 5 years at the Regional Dermatology Training Centre (RDTC) in Moshi, Tanzania. RESULTS There were a total of 1554 skin biopsy specimens. In 45% of cases, there were inflammatory diseases, most frequently lichenoid conditions. Cutaneous neoplasms represented 30.4% of all diagnoses, with Kaposi's sarcoma (KS) and, less frequently, squamous cell carcinoma (SCC) being the two most common neoplastic conditions. The latter also reflected the intensive management of persons with albinism in the RDTC. The distribution of histological diagnoses seemed to correlate with the overall clinical spectrum of cutaneous diseases managed in the RDTC. CONCLUSIONS In this African study inflammatory conditions are the main burden of skin diseases leading to a diagnostic biopsy. Our findings provide further evidence that KS, primarily related to the high prevalence of HIV infection is an epidemiological problem. Both SCC and basal cell carcinoma represent another relatively common malignant cutaneous neoplasms, reflecting the presence of specific populations at risk. The challenging spectrum of histological diagnoses observed in this specific African setting with basic working conditions shows that development of laboratory services of good standards and specific training in dermatopathology are urgently needed.

Skin cancers in renal transplant recipients: A description of the renal transplant cohort in Bern

BACKGROUND/AIMS: Skin tumours, in particular squamous-cell carcinomas (SCC), are the most common malignant conditions developing in transplant recipients. The aim of this study is to investigate the frequency and type of skin cancer in patients receiving immunosuppressive therapy after organ transplantation. METHODS: Multivariate logistic regression analysis was performed on data of 243 renal transplant patients who attended the dermatology outpatient clinic for the first time after transplantation in the period January 2002-October 2005. RESULTS: We found an increased risk of actinic keratosis (AK) and SCC in renal transplant recipients with a basal cell carcinoma (BCC) / SCC ratio of 1:7. Older patients had AK more frequently (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.06-1.15; p <0.0001) and SCC (OR 1.14, CI 1.07-1.22; p <0.0001) than younger patients. Men had AK (OR 0.19, CI 0.08-0.45; p = 0.0002) and SCC (OR 0.25, CI 0.07-0.89; p = 0.0332) more frequently than women. The duration of immunosuppressive therapy correlated significantly with the numbers of AKs (OR 1.15, CI 1.08-1.24; p <0.0001) and SCCs (OR 1.16, CI 1.05-1.28; p = 0.0025), and patients with fair skin had more AKs (OR 0.31, CI 0.14-1.24; p <0.0001) and SCCs (OR 0.11, CI 0.02-0.52; p = 0.0054) than darker skinned patients. We could not identify any specific immunosuppressive drug as a distinct risk factor for AK or non-melanoma skin cancer (NMSC). CONCLUSION: Skin cancers are increased in the renal transplant population. Main risk factors for skin cancers are fair skin type and long duration of immunosuppressive therapy. A follow-up programme is necessary for early detection of skin cancer and precancerous conditions. Preventive strategies should include specialist dermatological monitoring and self-examination.

Internet based health promotion campaign against skin cancer - Results of www.skincheck.ch in Switzerland

Conventional skin cancer prevention programs appeal to limited populations, and the middle aged male population responds less frequently. Our objective was to establish a complementary health promotion campaign tool for skin cancer prevention. Internet-based education, instruction for self assessment and teledermatological evaluation of skin lesions by an expert commission of dermatologists was used. Compliance and clinical diagnosis was assessed in a subgroup. 12,000 users visited the educational website. There was strong interest among the middle aged male population (53% (N = 262): male; mean age: 42). 28.5% of examined lesions (N = 494) were considered suspicious. Email requests, sent to the group whose lesions where considered suspicious, were answered by 46.0% of females (N = 29) and 59.7% of males (N = 46) with a female distribution predominantly in younger ages (52.6% of females with known age: < 30 years). Males were predominantly represented over 30 years (86.2% of all males). According to user's declarations, at least 8 (8.5%) malignant lesions (1 melanoma in situ, 1 squamous cell carcinoma, 4 basal cell carcinomas, 2 malignant lesions without declared diagnosis) were finally diagnosed by physicians. We conclude that internet-based, interactive, educational programs, in addition to existing health promotion campaigns, can enhance public participation in the middle aged male population in skin cancer prevention.

Differential expression of TGFbeta-stimulated clone 22 in normal prostate and prostate cancer

The transforming growth factor-beta (TGFbeta) superfamily and its downstream effector genes are key regulators of epithelial homeostasis. Altered expression of these genes may be associated with malignant transformation of the prostate gland. The cDNA array analysis of differential expression of the TGFbeta superfamily and functionally related genes between patient-matched noncancerous prostate (NP) and prostate cancer (PC) bulk tissue specimens highlighted two genes, namely TGFbeta-stimulated clone-22 (TSC-22) and Id4. Verification of their mRNA expression by real-time PCR in patient-matched NP and PC bulk tissue, in laser-captured pure epithelial and cancer cells and in NP and PC cell lines confirmed TSC-22 underexpression, but not Id4 overexpression, in PC and in human PC cell lines. Immunohistochemical analysis showed that TSC-22 protein expression in NP is restricted to the basal cells and colocalizes with the basal cell marker cytokeratin 5. In contrast, all matched PC samples lack TSC-22 immunoreactivity. Likewise, PC cell lines do not show detectable TSC-22 protein expression as shown by immunoblotting. TSC-22 should be considered as a novel basal cell marker, potentially useful for studying lineage determination within the epithelial compartment of the prostate. Conversely, lack of TSC-22 seems to be a hallmark of malignant transformation of the prostate epithelium. Accordingly, TSC-22 immunohistochemistry may prove to be a diagnostic tool for discriminating benign lesions from malignant ones of the prostate. The suggested tumour suppressor function of TSC-22 warrants further investigation on its role in prostate carcinogenesis and on the TSC-22 pathway as a candidate therapeutic target in PC.

Porcine ulcerative dermatitis syndrome in sows: a form of vesicular cutaneous lupus erythematosus?

Severe ulcerative lesions were observed in the skin of two sows in a herd of 540 hybrid sows. Annular to polycyclic, severe crusting dermal ulcerations were found on the abdomen and flanks; moderate lesions were also found at the base of the tail and on the perineum. The lesions were histologically characterised as cell-poor interface dermatitis and folliculitis, basal cell vacuolisation, vesicle formation at the dermal-epidermal junction and serocellular crusts. A subepidermal mild to moderate band, characterised as a mixed inflammatory infiltrate, was present. A test for antinuclear antibodies was negative; however, immunofluorescence testing revealed a linear pattern of IgG precipitation in the skin. Staphylococcus hyicus was demonstrated in the serocellular crusts of one sow. Treatment with antibiotics, topical antiseptics and corticosteroids did not improve the sows' condition. Porcine circovirus and porcine respiratory and reproductive syndrome virus were not isolated from samples taken at postmortem examination. The observed gross lesions, the absence of response to treatment and the exclusion of other skin diseases suggested that the sows were affected with porcine ulcerative dermatitis syndrome.

Histological review of skin cancers in African Albinos: a 10-year retrospective review.

BACKGROUND Skin cancer is rare among Africans and albinism is an established risk for skin cancer in this population. Ultraviolet radiation is highest at the equator and African albinos living close to the equator have the highest risk of developing skin cancers. METHODS This was a retrospective study that involved histological review of all specimens with skin cancers from African albinos submitted to The Regional Dermatology Training Center in Moshi, Tanzania from 2002 to 2011. RESULTS A total of 134 biopsies from 86 patients with a male to female ratio of 1:1 were reviewed. Head and neck was the commonest (n = 75, 56.0%) site affected by skin cancers. Squamous cell carcinoma (SCC) was more common than basal cell carcinoma (BCC) with a ratio of 1.2:1. Only one Acral lentiginous melanoma was reported. Majority (55.6%) of SCC were well differentiated while nodular BCC (75%) was the most common type of BCC. CONCLUSIONS Squamous cell carcinoma is more common than basal cell carcinoma in African albinos.

deltaNp63 has a role in maintaining epithelial integrity in airway epithelium.

The upper airways are lined with a pseudostratified bronchial epithelium that forms a barrier against unwanted substances in breathing air. The transcription factor p63, which is important for stratification of skin epithelium, has been shown to be expressed in basal cells of the lungs and its ΔN isoform is recognized as a key player in squamous cell lung cancer. However, the role of p63 in formation and maintenance of bronchial epithelia is largely unknown. The objective of the current study was to determine the expression pattern of the ΔN and TA isoforms of p63 and the role of p63 in the development and maintenance of pseudostratified lung epithelium in situ and in culture. We used a human bronchial epithelial cell line with basal cell characteristics (VA10) to model bronchial epithelium in an air-liquid interface culture (ALI) and performed a lentiviral-based silencing of p63 to characterize the functional and phenotypic consequences of p63 loss. We demonstrate that ΔNp63 is the major isoform in the human lung and its expression was exclusively found in the basal cells lining the basement membrane of the bronchial epithelium. Knockdown of p63 affected proliferation and migration of VA10 cells and facilitated cellular senescence. Expression of p63 is critical for epithelial repair as demonstrated by wound healing assays. Importantly, generation of pseudostratified VA10 epithelium in the ALI setup depended on p63 expression and goblet cell differentiation, which can be induced by IL-13 stimulation, was abolished by the p63 knockdown. After knockdown of p63 in primary bronchial epithelial cells they did not proliferate and showed marked senescence. We conclude that these results strongly implicate p63 in the formation and maintenance of differentiated pseudostratified bronchial epithelium.

European Dermatology Forum Guidelines on topical photodynamic therapy

Topical photodynamic therapy (PDT) is a widely approved therapy for actinic keratoses, squamous cell carcinoma in-situ, superficial and certain thin basal cell carcinomas. Recurrence rates are typically equivalent to existing therapies, although inferior to surgery for nodular basal cell carcinoma. PDT can be used both as a lesional or as a field therapy and has the potential to delay/reduce the development of new lesions. PDT has also been studied for its place in the treatment of, as well as its potential to prevent, superficial skin cancers in immune-suppressed patients, although sustained clearance rates are lower than for immunocompetent individuals. Many additional indications have been evaluated, including photo-rejuvenation and inflammatory and infective dermatoses. This S2 guideline considers all current and emerging indications for the use of topical photodynamic therapy in Dermatology, prepared by the PDT subgroup of the European Dermatology Forum guidelines committee. It presents consensual expert recommendations reflecting current published evidence. An unabridged version of this guideline is available online at: http://www.euroderm.org/edf/index.php/edf-guidelines.

Extensive extranodal metastases of basal-like breast cancer with predominant myoepithelial spindle cell differentiation

A differentiation towards myoepithelial cells has been demonstrated in several types of lesions in the breast. These include multifocal myoepitheliomatosis, the rare mixed tumor or pleomorphic adenoma, adenoid cystic carcinoma, adenomyoepithelioma and myoepithelial carcinoma (malignant myoepithelioma). Myoepithelial carcinoma is the only lesion purely composed of myoepithelial cells. All these tumors are benign and/or of low-grade malignancy, with the exception of malignant myoepithelioma. In contrast to the statement of the current World Health Organization (WHO), recent studies have reported that regional and distant metastases may occur in about 50% of pure myoepithelial carcinomas. The presented case of a breast carcinoma with dominant myoepithelial/spindle cell differentiation in a 58-year-old woman is an excellent example to document the highly aggressive biological behavior of this tumor phenotype. Despite an extensive chemotherapy and radiotherapy, the tumor was rapidly progressive, forming a finally exulcerating local tumor relapse and widespread metastases to the myocardium, lungs, liver, kidneys and skin. Similarities in morphology and biological behavior compared to patients with "triple-negative" (hormone receptor and Her2) monophasic sarcomatoid carcinomas and pure spindle cell sarcomas are discussed.

Detection of Merkel cell polyomavirus in epidermodysplasia-verruciformis-associated skin neoplasms

BACKGROUNd: Epidermodysplasia verruciformis (EV) is a rare genodermatosis that is characterized by susceptibility to infection with specific human papillomavirus (HPV) genotypes. Among polyomaviruses, the novel Merkel cell polyomavirus (MCPyV) has been found in different epithelial skin neoplasias.