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Eggert Stockfleth

Publications and source records attributed to Eggert Stockfleth.

At least 19 recordsLinked to original sources
PubMed2006

Identification of differentially expressed genes in cutaneous squamous cell carcinoma by microarray expression profiling.

BACKGROUND: Carcinogenesis is a multi-step process indicated by several genes up- or down-regulated during tumor progression. This study examined and identified differentially expressed genes in cutaneous squamous cell carcinoma (SCC). RESULTS: Three different biopsies of 5 immunosuppressed organ-transplanted recipients each normal skin (all were pooled), actinic keratosis (AK) (two were pooled), and invasive SCC and additionally 5 normal skin tissues from immunocompetent patients were analyzed. Thus, total RNA of 15 specimens were used for hybridization with Affymetrix HG-U133A microarray technology containing 22,283 genes. Data analyses were performed by prediction analysis of microarrays using nearest shrunken centroids with the threshold 3.5 and ANOVA analysis was independently performed in order to identify differentially expressed genes (p < 0.05). Verification of 13 up- or down-regulated genes was performed by quantitative real-time reverse transcription (RT)-PCR and genes were additionally confirmed by sequencing. Broad coherent patterns in normal skin vs. AK and SCC were observed for 118 genes. CONCLUSION: The majority of identified differentially expressed genes in cutaneous SCC were previously not described.

Adolescent↗
PubMed2006

Phylogenetic analysis of beta-papillomaviruses as inferred from nucleotide and amino acid sequence data.

Human papillomaviruses (HPV) of the beta-group seem to be involved in the pathogenesis of non-melanoma skin cancer. Papillomaviruses are host specific and are considered closely co-evolving with their hosts. Evolutionary incongruence between early genes and late genes has been reported among oncogenic genital alpha-papillomaviruses and considerably challenge phylogenetic reconstructions. We investigated the relationships of 29 beta-HPV (25 types plus four putative new types, subtypes, or variants) as inferred from codon aligned and amino acid sequence data of the genes E1, E2, E6, E7, L1, and L2 using likelihood, distance, and parsimony approaches. An analysis of a L1 fragment included additional nucleotide and amino acid sequences from seven non-human beta-papillomaviruses. Early genes and late genes evolution did not conflict significantly in beta-papillomaviruses based on partition homogeneity tests (p > or = 0.001). As inferred from the complete genome analyses, beta-papillomaviruses were monophyletic and segregated into four highly supported monophyletic assemblages corresponding to the species 1, 2, 3, and fused 4/5. They basically split into the species 1 and the remainder of beta-papillomaviruses, whose species 3, 4, and 5 constituted the sistergroup of species 2. beta-Papillomaviruses have been isolated from humans, apes, and monkeys, and phylogenetic analyses of the L1 fragment showed non-human papillomaviruses highly polyphyletic nesting within the HPV species. Thus, host and virus phylogenies were not congruent in beta-papillomaviruses, and multiple invasions across species borders may contribute (additionally to host-linked evolution) to their diversification.

Amino Acid Sequence↗
PubMed2006

Identification of dysregulated genes in cutaneous squamous cell carcinoma.

Carcinogenesis is a multi-step process resulting from the accumulation of genetic mutations and subsequently leading to dysregulated genes, but the number and identity of differentially expressed genes in cutaneous squamous cell carcinoma (SCC) is unknown at present. In order to identify dysregulated genes, we examined the relative mRNA expression present in cutaneous SCC and its precursor lesion actinic keratosis (AK) by comparison to normal skin. Snap frozen biopsies from 20 specimens of normal skin, 10 AK, and 10 cutaneous SCC were examined. Total-RNA was extracted, reversely transcribed, and 14 genes were investigated using gene-specific intron-flanking primers and quantitative real-time reverse transcription PCR. Specificity was confirmed by sequencing of the PCR amplicons. Ten of 14 genes were significantly dysregulated in AK and/or cutaneous SCC by comparison to normal skin. The genes CNN2, COX4I1, COX5B, COX7C, CRLF3, CTSC, NDRG1, and LMNA showed increased expression in skin cancer (p < 0.02), while RPL15 and LGTN were down-regulated (p < 0.03). The genes differentially expressed during skin carcinogenesis may prove useful in order to understand the origin and progression of cutaneous SCC and for diagnostic approaches.

Aged↗
PubMed2005

Multiple disseminated large-cell acanthomas of the skin associated with human papillomavirus type 6.

Cutaneous acanthomas encompass many clinically distinct types. We describe a patient with multiple nodules on the skin of the upper limbs which were histologically diagnosed as large-cell acanthomas. Further analysis revealed, surprisingly, the presence of human papillomavirus (HPV) type 6 within these lesions. HPV type 6 should therefore be considered an important cofactor in the pathogenesis of large-cell acanthomas.

Acanthoma↗
PubMed2004

High sensitivity and reproducibility of immunohistochemistry with microagitation.

We examined the practicability, reproducibility and analytical sensitivity of classical immunohistochemistry (IHC) and IHC with microagitation. Two monoclonal antibodies, Ki-67 (proliferation marker) and p53 (tumor suppressor marker), were used. Consecutive paraffin sections of biopsies of suspicious lesions of patients with non-melanoma skin cancer were used in the study. Reproducibility was examined using specimens from four patients in three independent experiments with antibodies against Ki-67 and p53. Analytical sensitivity of the two methods was determined using serial dilutions in two independent experiments. IHC with microagitation could be carried out without destroying the tissue. The new technique was consistent and reproducible, and no background staining was observed. The primary antibodies Ki-67 and p53 could be used at higher dilutions (four to ten times) with microagitation compared with classical IHC. Microagitation can be used for immunohistochemistry; it was reproducible, highly sensitive, and antibodies could be used at higher dilutions. Further analyses with other antibodies using this technique are warranted.

Biopsy↗
PubMed2004

Specialty clinics for the dermatologic care of solid-organ transplant recipients.

BACKGROUND: Solid-organ transplant recipients constitute a complex patient population that experiences numerous and aggressive skin cancers. Proactive, comprehensive, ongoing, and effective dermatologic care of these patients is a necessity. OBJECTIVE: The objective of this study was to emphasize the need for organized dermatologic care for transplant recipients and to collect and present various proactive paradigms established in and designed for different practice settings to manage organ transplant recipients at high risk for skin cancer. METHODS: Information about practice setting, patient demographics, and the care model used was obtained through questionnaires sent to a selection of 12 physicians known to care for transplant recipients in various practice settings. RESULTS: All 12 physicians completed the questionnaire. The organized dermatologic care of transplant recipients occurs in three basic clinic settings: multidisciplinary transplant clinics, designated dermatology transplant subspecialty clinics, and integration of transplant recipient care within existing dermatology clinics. CONCLUSIONS: Various practice settings offer both advantages and disadvantages in providing preventive and therapeutic care of organ transplant recipients at risk for skin cancer. Regardless of the clinic design used, an organized and firmly established clinic model to allow proactive and ongoing care for these patients is important for education, prevention, and early intervention.

Dermatology↗
PubMed2004

Human papillomaviruses in transplant-associated skin cancers.

BACKGROUND: Human papillomavirus (HPV) infection has been suggested to be involved in the development of nonmelanoma skin cancer, the most common malignancy after solid-organ transplantation. OBJECTIVE: The objective of this study was to analyze the prevalence of different HPV types in squamous cell carcinomas (SCC) and basal cell carcinomas (BCC) of transplant recipients and nonimmunosuppressed patients. METHODS: To include the complete spectrum of HPV types in skin lesions, a comprehensive polymerase chain reaction assay with five different primer combinations was used. RESULTS: For SCC, HPV DNA was detected more frequently in tumors of transplant recipients (12/16, 75%) than of nonimmunosuppressed patients (7/19, 37%). In contrast, the HPV detection rate was similar in BCC specimens (4/8 or 50% in transplanted patients; 27/56 or 48% in nonimmunosupressed patients). Overall, 22 different HPV types were identified. HPV types 5 and 8 were detected predominately in SCC from transplant recipients. The amount of viral DNA was slightly higher in SCC of transplanted than in nonimmunosuppressed patients, but much lower than in both cutaneous and genital warts. CONCLUSIONS: Cutaneous infections with HPV5 and HPV8 may represent an increased risk for SCC development in transplant recipients. The mechanisms by which these viruses may contribute to skin cancer development still remain unclear.

Adult↗
PubMed2004

Human papillomavirus and overexpression of P16INK4a in nonmelanoma skin cancer.

BACKGROUND: P16INK4a overexpression has been identified as a specific biomarker in high-risk human papillomavirus (HPV)-infected cervical (pre)cancer lesions. OBJECTIVE: To evaluate the overexpression of this cyclin-dependent kinase inhibitor in skin tumors depending on HPV infections, we analyzed normal skin, benign skin disease, and skin cancer specimens. METHODS: Biopsies of 23 patients with normal histology (3), psoriasis (2), verrucae vulgaris (2), actinic keratoses (5), squamous cell carcinoma (SCC) in situ (3), Bowen's carcinoma (1), and SCC (7) were analyzed. Specimens of 23 patients were immunostained using the monoclonal antibody E6H4 specific for p16INK4a. HPV status was assessed by a polymerase chain reaction (PCR) system to detect all currently known HPV types. MY (MY09/MY11 and MYN9/MYN10)-, CP (CP65/CP70 and CP66/CP69)-nested PCR, and three single PCR methods CN1, CN3, and CN4 were used in a first step, and HPV typing was performed by restriction fragment length polymorphism analysis. Only beta-globin-positive patients were included in this study. RESULTS: HPV DNA was detected in all actinic keratoses, SCC in situ, Bowen's carcinoma, and SCC, in 50% (one of two) of verrucae vulgaris, in 66% (two of three) of normal skin, and in none of two psoriasis. P16INK4a expression was not detected in normal skin, psoriasis, and verrucae vulgares. Overexpression of p16INK4a was detected in a subset of dysplastic cells (10% to 80%) of all skin (pre)cancer lesions such as actinic keratoses, SCC in situ, Bowen's carcinoma, and SCC infected with HPV independent of sun exposure. CONCLUSION: P16INK4a appears to be overexpressed in a portion of dysplastic cells from actinic keratoses and SCC. Further studies to examine the association of HPV infection and the overexpression of p16INK4a are warranted.

Aged↗
PubMed2004

Comparative epidemiology and pathogenic factors for nonmelanoma skin cancer in organ transplant patients.

BACKGROUND: Organ transplantation has been performed for almost 40 years with steadily increasing success regarding long-time survival of the graft as well as quality of life for the patient. An increase of skin cancers as a consequence of the lowered cellular immune response seems to parallel the overall increased survival rate of organ transplant recipients. Against the background of chronic immunosuppression, known risk factors like the amount of sun exposure before and after transplantation and oncogenic viruses as well as the genetic background and place of residence (latitude) are strongly related with the increased skin cancer incidence. The goal of this review is to compare the epidemiologic prevalence of nonmelanoma skin cancer between various geographic locations and to highlight pathogenesis factors. METHODS: This study was based on a review of the current literature. RESULTS: The increasing incidence of nonmelanoma skin cancer paralleling a prolonged survival of patients after organ transplantation represents a significant reason for morbidity and long-term mortality in organ transplant recipients worldwide. The incidence of nonmelanoma skin cancer in liver, kidney, and heart transplant recipients varies from 1.5% to 22%, 2% to 24%, and 6% to 34%, respectively, within 5 years of transplantation depending on geographic location and other pathogenesis factors. Ultraviolet radiation (UVR) as well as immunosuppressant therapy are crucial risk factors regarding the induction and progression of skin cancer. UVR is related to the induction of DNA damage as well as interference with Langerhans cell antigen presentation and a TH1-TH2 shift induced via release of IL-10. Whereas the overall duration of immunosuppression and the accumulative dosage applied are relevant measures in the pathogenesis of an increased tumor risk, individual differences between specific immunosuppressive agents are more difficult to assess. CONCLUSIONS: Multiple international studies assess risk factors and pathophysiology of skin cancer in organ transplant patients, with variable results in the literature. Large multicenter studies with thorough multivariant analysis may provide useful information for center-independent analysis of pathogenesis factors for transplant-related skin cancer.

Australia↗
PubMed2004

Guidelines for the management of squamous cell carcinoma in organ transplant recipients.

BACKGROUND: Solid-organ transplant recipients have a high incidence of cutaneous squamous cell carcinoma (SCC) and often develop multiple and aggressive tumors. There are few published studies or reviews, which provide guidance to the clinician in the treatment of these patients. OBJECTIVE: The objective was to develop useful clinical guidelines for the treatment of skin cancer in organ transplant recipients (OTRs). METHODS: The members of the Guidelines Committee of the International Transplant-Skin Cancer Collaborative (ITSCC) carried out a computerized search utilizing the databases of the National Library of Medicine for reports in the literature on SCC in OTRs. These reports were collectively examined by the group and combined with experiences from the members' clinical practices in the development of the guidelines. RESULTS: More than 300 articles relating to SCC in OTRs were reviewed. In general, reports concerning the prevention and treatment of SCC in OTRs are of individual cases or small case series. They are retrospective in nature, statistically nonrigorous, and lack the complete epidemiologic data necessary to derive definitive conclusions. Combining these studies and collective clinical experience, however, is at present the best available method for devising guidelines for the treatment of SCC in OTRs. CONCLUSION: Guidelines developed for the treatment of skin cancer in OTRs, supported by the best available data and collective clinical experience, may assist in the management of OTRs with SCC. The development of clinical pathways and complete documentation with rigorous prospective study is necessary to improve and refine future guideline development.

Carcinoma, Squamous Cell↗
PubMed2003

Association of human papillomavirus infections with cutaneous tumors in immunosuppressed patients.

Besides immunosuppression and UV radiation, human papillomavirus (HPV) infection was also suggested to be involved in the development of non-melanoma skin cancer, the most common malignancy after transplantation. In this study we used a comprehensive PCR assay to analyze the prevalence of individual HPV types in different skin lesions from transplant and non-transplant patients. HPV DNA was detected more frequently in squamous cell carcinomas (SCCs) of transplant recipients (75%) than the same lesion was in non-immunosuppressed patients (47%). Similar HPV prevalences were found in cutaneous warts (91% vs 94%), pre-malignant skin tumors (38% vs 36%), and normal skin specimens (17% vs 16%) of both patient populations. Overall, more than 40 different HPV types were identified. HPV types 5 and 8 were found more frequently in SCCs (26%) than in pre-cancerous (5%) or benign lesions (1%). All HPV 5- and HPV 8-positive SCCs were from immunosuppressed patients, indicating that infection with HPV 5 and HPV 8 may present an increased risk of SCC development in these patients.

Base Sequence↗
PubMed2002

A randomized, double-blind, vehicle-controlled study to assess 5% imiquimod cream for the treatment of multiple actinic keratoses.

BACKGROUND: Actinic keratoses (AKs) are precancerous epidermal lesions found most frequently on areas of the skin exposed to the sun. Several case studies published recently have indicated that 5% imiquimod cream, currently licensed for the treatment of genital warts, may be an effective treatment for AK. OBJECTIVE: To assess the efficacy and safety of imiquimod for the treatment of AK. DESIGN: Patients in this randomized, double-blind, vehicle-controlled study applied 5% imiquimod cream or vehicle to AK lesions 3 times per week for a maximum of 12 weeks or until lesions had resolved. In the event of an adverse reaction, application of imiquimod was reduced to 1 or 2 times per week. Rest periods were also allowed if necessary. SETTING: A specialized outpatient dermatology clinic within a state-funded hospital in Germany. PATIENTS: The study population was aged 45 to 85 years. Of 52 patients screened, 36 men and women with AK confirmed by histological diagnosis were enrolled. Patients were excluded from the study if they did not have a histological diagnosis for AK, if they were older than 85 years, or if they did not comply with the protocol. All patients had responded to a notice asking for volunteers. MAIN OUTCOME MEASURES: The number and appearance of lesions were evaluated before, during, and after treatment. All adverse effects were recorded. RESULTS: Lesions treated with 5% imiquimod cream were clinically cleared in 21 (84%) of 25 patients and partially cleared in 2 (8%). Clearance was histologically confirmed 2 weeks after the last application of imiquimod in all patients clinically diagnosed as lesion free. Only 10% of patients treated with imiquimod were clinically diagnosed with recurrence 1 year after treatment. No reduction in the size or number of AK lesions was observed in vehicle-treated patients. Adverse effects reported by patients treated with imiquimod included erythema, edema, induration, vesicles, erosion, ulceration, excoriation, and scabbing. However, imiquimod was well tolerated since all patients completed the 12-week treatment. Only a few, mild adverse reactions to the vehicle cream were reported. CONCLUSION: Application of 5% imiquimod cream for 12 weeks is an effective and well-tolerated treatment for AK.

Adjuvants, Immunologic↗