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Matthias Volkenandt

Publications and source records attributed to Matthias Volkenandt.

15 recordsLinked to original sources
PubMed2006

Variations of the melanocortin-1 receptor and the glutathione-S transferase T1 and M1 genes in cutaneous malignant melanoma.

Variations in the melanocortin-1 receptor (MC1R) and in the glutathione-S transferase genes mu1 (GSTM1) and theta 1 (GSTT1) have been reported to influence UV sensitivity and melanoma risk. MC1R is one of the major genes that determine skin pigmentation because the melanocortin-1 receptor regulates eumelanin synthesis. GSTT1 and GSTM1 are enzymes expressed in the skin that detoxify products of oxidative stress reactions caused by UV irradiation. In this study variations in the MC1R, GSTM1 and T1 genes were analyzed in 347 healthy subjects and 322 patients with cutaneous malignant melanoma by direct cycle sequencing, RFLP and multiplex PCR. Important phenotypic characteristics of the study participants were obtained to assess whether genetic associations occurred independently of phenotypic risk factors for melanoma. We found an association of the MC1R D84E and R151C polymorphisms with melanoma (odds ratios for carriage of the rare allele 4.96, 95% CI [1.06-23.13], P = 0.032, and 1.69, 95% CI [1.12-2.55], P = 0.013, respectively). Melanoma risk increased with the number of variant MC1R alleles carried by an individual (P = 0.003). In a multivariate model, however, only the D84E polymorphism influenced melanoma risk independently of the risk factors fair skin type, high nevus count and high age (P = 0.047). There was no effect of homozygous GST M1 or T1 deletions on melanoma risk. In contrast to previous data, there was no evidence that GSTM1 deficiency influences melanoma risk in the subgroup of individuals with red or blond hair.

Adult↗
PubMed2006

Variations in the peroxisome proliferator-activated receptor-gamma gene and melanoma risk.

There is strong evidence to suggest that the peroxisome proliferator-activated receptor (PPAR)-gamma, a member of the nuclear receptor family of transcriptional regulators, mediates tumor suppressive activities in a variety of human cancers. Recently, PPARgamma agonists were found to inhibit growth of melanoma cell lines. Here, we tested the possibility that variations in the gene encoding PPARgamma (PPARG) influence melanoma risk. Two variations of PPARG (P12A[rs1801282] and C161T [rs3856806]) were investigated in two independent case-control studies with a total of 832 melanoma patients and 790 control individuals. In the first study, homozygous carriers of the rare *T allele of the C161T polymorphism in exon 6 of PPARG were significantly more common among patients with melanoma than among healthy subjects (6.0 vs. 2.0%; P=0.0096) and this association was independent of clinical risk factors such as skin type and nevus count (odds ratio 5.18; 95% confidence interval 1.68-15.96; P=0.0041). This finding, however, could not be replicated in the second case-control study. We therefore conclude that the investigated PPARG polymorphisms are not likely to constitute a significant risk factor for the development of melanoma among German Caucasians.

Adolescent↗
PubMed2006

Long-term survival benefit after adjuvant treatment of cutaneous melanoma with dacarbazine and low dose natural interferon alpha: A controlled, randomised multicentre trial.

In a prospective, controlled, randomised, multicentre study 252 patients with totally resected cutaneous melanoma (248 in stage II-III and 4 in stage IV) were either treated with two doses of dacarbazine (DTIC) followed by a 6-month treatment with 3 MU thrice weekly of highly purified natural interferon-alpha (n = 128; arm A) or received no adjuvant treatment (n = 124; arm B). Treatment was well tolerated. After a median follow-up of 8.5 years ITT analysis showed that the difference in survival was statistically significant with respect to melanoma-related deaths (HR = 0.65, CI = 0.46-0.97, p = 0.022) and close to significance with respect to overall survival (HR 0.71, CI 0.49-1.00, p = 0.052). The risk reduction of melanoma-associated death, calculated by Cox proportional hazards modelling, after adjusting for identified predictive variables, was almost 50% (p = 0.002). The overall efficacy of the treatment appeared to be mainly attributable to effects observed in patients with deep and/or metastasizing tumours (HR 0.60, CI 0.40-0.90, p = 0.013).

Adult↗
PubMed2005

Assessment of 3 xeroderma pigmentosum group C gene polymorphisms and risk of cutaneous melanoma: a case-control study.

Individuals with the rare DNA repair deficiency syndrome xeroderma pigmentosum (XP) are sensitive to the sun and exhibit a 1000-fold increased risk for developing skin cancers, including cutaneous melanoma. Inherited polymorphisms of XP genes may contribute to subtle variations in DNA repair capacity and genetic susceptibility to melanoma. We investigated the role of three polymorphic alleles of the DNA repair gene XPC in a hospital-based case-control study of 294 Caucasian patients from Germany who had cutaneous melanoma and 375 healthy cancer-free sex-matched Caucasian control subjects from the same area. We confirmed that the XPC intron 9 PAT+, intron 11 -6A, and the exon 15 2920C polymorphisms are in a linkage disequilibrium. Only 1.6% of the 669 donors genotyped were discordant for these three polymorphisms. The allele frequencies (cases: controls) were for intron 9 PAT+ 41.7%:36.9%, for intron 11 -6A 41.8%:37.0% and for exon 15 2920C 41.3%:37.3%. Using multivariate logistic regression analyses to control for age, skin type and number of nevi, the three polymorphisms were significantly associated with increased risks of melanoma: OR 1.87 (95% CI: 1.10-3.19; P = 0.022), OR 1.83 (95% CI: 1.07-3.11; P = 0.026), and OR 1.82 (95% CI: 1.07-3.08; P = 0.026), respectively. Exploratory multivariate analyses of distinct subgroups revealed that these polymorphisms were associated with increased risks for the development of multiple primary melanomas (n = 28). The results of our case-control study support the hypothesis that the intron 9 PAT+, intron 11 -6A and exon 15 2920C haplotype may contribute to the risk of developing cutaneous melanoma by increasing the rate of an alternatively spliced XPC mRNA isoform that skips exon 12 and leads to reduced DNA repair. Our results should be validated in independent samples in order to guard against false positive findings.

Adult↗
PubMed2005

No association between three xeroderma pigmentosum group C and one group G gene polymorphisms and risk of cutaneous melanoma.

Xeroderma pigmentosum (XP) patients exhibit a 1000-fold increased risk for developing skin cancers including malignant melanoma. We investigated the role of three variant alleles of the DNA repair gene XPC and one variant allele of the XPG gene in a hospital-based case-control study of 294 Caucasian patients from Germany with malignant melanoma and 375 healthy control individuals from the same area matched by sex. The polymorphisms G1580A (XPC exon 8; Arg492His), T1601C (XPC exon 8; Val499Ala), G2166A (XPC exon 10; Arg687Arg), and C3507G (XPG exon 15; Asp1104His) were not in linkage disequilibrium. The allele frequencies (cases: controls) were for 1580A 6.29%: 5.63%, for 1601C 79.08%: 78.28%, for 2166A 26.19%: 28.13%, and for 3507G 79.86%: 78.61%. We found no association of the homozygous 1580A, 1601C, 2166A, and 3507G genotypes with increased risks of melanoma: OR 1.254 (95% CI: 0.486-3.217), OR 1.108 (95% CI: 0.629-1.960), OR 0.817 (95% CI: 0.490-1.358), and OR 1.168 (95% CI: 0.670-2.044), respectively. Exploratory analyses of subgroups of melanoma patients compared to all controls indicated no association of these genotypes with increased risks for development of multiple primary melanomas (n = 28), a negative family history for melanoma (n = 277), melanomas in individuals with a low number of nevi (n = 273), melanomas in individuals older than 55 years (n = 142), and melanomas thicker than 1 mm (n = 126).

Amino Acid Substitution↗
PubMed2004

Correlation between sICAM-1 and depressive symptoms during adjuvant treatment of melanoma with interferon-alpha.

Interferon-alpha (IFN-alpha) treatment is frequently complicated by symptoms of depression. The mechanism by which peripherally administered IFN-alpha enters and modulates the central nervous system remains unclear. The cell adhesion molecule ICAM-1 is involved in the regulation of blood-brain barrier (BBB) permeability. ICAM-1 expression was shown to increase during IFN-alpha treatment and recently the expression of ICAM-1 on vascular endothelial cells in the brain was found to be correlated with the development of depression. We therefore hypothesized that soluble ICAM-1 may be involved in the development of IFN-alpha associated depression. In a prospective study, serum levels of soluble ICAM-1 (double sandwich ELISA test) and symptoms of depression (SDS) were measured in 48 patients with malignant melanoma before and during adjuvant IFN-alpha treatment. Both, depression scores and the serum levels of sICAM-1 significantly increased after three months of IFN-alpha treatment compared to baseline levels (p < .001). Patients who developed depression (SDS-index scores > or = 50) after three months of treatment had higher sICAM-1 levels compared to non-depressed patients. Furthermore, sICAM-1 levels were positively correlated with SDS values (r = .367, p = .018). Our data provides evidence for an association between the induction of sICAM-1 and the development of symptoms of depression during IFN-alpha treatment, possibly by enhancing BBB-permeability.

Adjuvants, Immunologic↗
PubMed2004

Seasonal variations in the diagnosis of cutaneous melanoma.

Seasonal patterns in diagnosis were examined in 7836 patients with cutaneous melanoma (clinical stage I and II) documented at the Department of Dermatology and Allergology at Ludwig-Maximilian-University in Munich, Germany, between 1977 and 2000. Of these patients, 2362 were first given a diagnosis in the summer months (June-August) and 1757 were first given a diagnosis in the winter months (December-February). A summer-to-winter ratio was determined for sex, age, anatomic tumor site, histopathologic subtype, and tumor thickness. The summer-to-winter ratio was 1.34 (95% confidence interval: 1.27-1.43) for all patients, with a ratio of 1.22 (95% confidence interval: 1.12-1.33) for men and 1.47 (95% confidence interval: 1.35-1.60) for women. The frequency of diagnosis of cutaneous melanoma was seasonal for all age classes, for all anatomic tumor sites, for all histopathologic subtypes except acrolentiginous melanomas, and for melanomas with a tumor thickness <3.0 mm. Comparing subgroups of the above-mentioned clinical and histopathologic parameters, significant differences could be observed for sex and anatomic tumor site. On the basis of this data, possible explanations for the diagnostic summer peak may be a greater awareness as a result of clothing habits in summertime or because of incurred sunburns in patients with skin type I and II, and the influence of public-health campaigns usually performed at the beginning of summer.

Aged↗
PubMed2003

Loss of expression of tuberin and hamartin in tuberous sclerosis complex-associated but not in sporadic angiofibromas.

BACKGROUND: Angiofibromas occur sporadically, and they develop in most patients with tuberous sclerosis complex (TSC), which is associated with alterations of the tumor suppressor genes TSC1 or TSC2. Loss of tuberin, the protein product of TSC2, has been shown in the interstitial fibroblast compartment of TSC-associated angiofibromas. It is unclear whether there is also a loss of hamartin, the product of TSC1 in TSC-associated and sporadic angiofibromas. METHODS: The expression of hamartin and tuberin was analyzed by immunohistochemistry in 59 TSC-associated and 12 sporadic angiofibromas using affinity-purified antibodies. RESULTS: Loss of expression of both tuberin and hamartin was detected in 14 angiofibromas, loss of only tuberin in three, and loss of only hamartin in four TSC-associated angiofibromas; but there was no loss in the sporadic angiofibromas. Only the interstitial cells, but not the vascular cells, showed a loss of expression of tuberin or hamartin. CONCLUSIONS: Loss of tuberin or hamartin occurred in a minority of the TSC-linked angiofibromas, but not in the sporadic angiofibromas. The absence of both tuberin and hamartin in some of the tumors suggests that the stability of tuberin and hamartin, which are believed to form an active complex in vivo, is negatively affected by the absence of either of the partners.

Angiofibroma↗
PubMed2003

Value of ultrasonography compared with physical examination for the detection of locoregional metastases in patients with cutaneous melanoma.

In several studies the early detection of locoregional metastases in patients with cutaneous melanomas has been shown to be of prognostic value. Physical examination alone often fails to detect locoregional metastases or cannot unambiguously classify palpable lymph nodes. This study aimed to evaluate the usefulness of high resolution ultrasonography for the early detection of locoregional metastases and to compare the sensitivity and specificity of ultrasound and physical examination. A prospective study was performed between January 1997 and June 1999 in 1395 patients (721 men and 674 women) with invasive cutaneous melanoma, treated and followed up at the Department of Dermatology and Allergology, Ludwig-Maximilian-University, Munich, Germany. A total of 2650 physical and ultrasound examinations of lymphatic drainage areas were performed, and lesions suspicious for metastases were excised and diagnosed by histopathology. The results of physical and ultrasound examinations were compared. Of the 2650 ultrasound examinations, metastases were suspected in 153, whereas 290 of the 2650 physical examinations were suspicious for metastatic disease. A total of 168 patients with suspicious lesions underwent surgery; histopathological examination revealed 112 melanoma metastases and 56 other diagnoses, including one second malignancy, one neurinoma, one haemangioma and 54 reactive lymph nodes. Ultrasonographic diagnosis of melanoma metastases had a sensitivity of 92.2% and a specificity of 98.2%, whereas diagnosis by physical examination had a sensitivity of only 51.3% and a specificity of 90.9%. Thus ultrasound examination was found to be highly effective and superior to physical examination for the early detection of locoregional melanoma metastases.

Adolescent↗
PubMed2002

[Skin cancer].

The current status, clinic, causes and prevention strategies of malignant tumours of the skin are described. Dermatologists, physicians and health professionals have made tremendous efforts to improve the public education and early detection of these tumours especially during the last decade. Further campaigns and continual medical education are demanded to continue this improvement for patients and public health system.

Basal Cell Carcinoma↗
PubMed2002

Improved differentiation of benign and malignant lymphadenopathy in patients with cutaneous melanoma by contrast-enhanced color Doppler sonography.

OBJECTIVE: To evaluate whether administration of a D-galactose-based signal enhancer is useful in color Doppler sonography (CDS) for better detection of vascularity patterns, which may help to differentiate malignant from benign lymph nodes in patients with cutaneous melanomas. DESIGN: Comparison of B-mode sonography, native CDS, and signal-enhanced CDS. SETTING: Department of Dermatology and Allergology, Ludwig-Maximilians-University, Munich, Germany. PATIENTS: Twenty examinations in 19 patients (median age, 60 years; 10 men) who presented with echo-poor structures suggestive of lymphadenopathy in B-mode sonography during follow-up for cutaneous melanomas. INTERVENTIONS: Histopathologic and follow-up examinations; documentation by color prints. MAIN OUTCOME MEASURES: Frequency of detection and description of different lymph node vascularity patterns in signal-enhanced CDS. RESULTS: Signal-enhanced CDS revealed additional information about vascularization of lymph node metastases, reactive lymph nodes, hematomas, and seromas, which was helpful for the differential diagnosis in 15 of 20 examinations. For lymph node metastases, signal enhancement facilitated the detection of accessory peripheral vessels in most investigations. Concerning reactive lymph nodes, hilar vessels in part with branching to the lymph node periphery could be identified only after application of the contrast enhancer in most patients. Quantitative variables could not be measured in all cases and did not help to differentiate between malignant and reactive lymph nodes. CONCLUSIONS: Administration of a D-galactose-based signal enhancer for CDS in patients with cutaneous melanomas can help to differentiate malignant from reactive lymph nodes, hematomas, or seromas. However, these promising results require confirmation in a prospective multicenter study.

Adult↗
PubMed2002

Cutaneous melanoma in childhood and adolescence: an analysis of 36 patients.

Analysis of data of 6931 patients with cutaneous melanoma seen at the Department of Dermatology and Allergology at the Ludwig-Maximilians-University of Munich between 1977 and 1998 identified 36 patients in whom cutaneous melanomas developed during childhood or adolescence (age <18 years). Clinical courses of all patients and histopathologic characteristics of the lesions were reviewed. Seventeen patients were boys and 19 patients were girls. The median ages of the boys and girls were 15 and 16 years, respectively (range, 2-17 years). Thirty-one patients presented with nonmetastatic primary melanomas and 5 patients presented with metastatic melanoma. Forty-seven percent of the primary lesions were associated with a nevus (22% with congenital nevi and 25% with acquired nevi). Tumor thickness ranged from 0.24 to 7.0 mm, with a median of 1.29 mm (mean, 1.67 mm). All patients with primary melanomas received surgical therapy; patients with metastatic disease received chemotherapy, radiation therapy, or both. Relative 5-year survival was 87.5% for the group of patients younger than 18 years. Similar to experience in adult patients, survival strongly correlated with tumor thickness and clinical stage at the time of diagnosis. The data emphasize that a high index of suspicion for cutaneous melanoma is needed by clinicians assessing melanocytic lesions in children and adolescents for early diagnosis. Reduction of the melanoma mortality rate in children and adolescents will be achieved through identification of patients at increased risk.

Adolescent↗