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Claus Garbe

Publications and source records attributed to Claus Garbe.

At least 55 records · Page 3Linked to original sources

Dermatofibrosarcoma protuberans--an update.

Dermatofibrosarcoma protuberans (DFSP) is a rare fibroblastic skin tumor of intermediate malignancy. Its pathogenesis has not yet been fully clarified. Recent basic genetic research has shown chromosomal translocations, generally termed "ring chromosomes", in DFSP. These arise from a fusion of chromosome regions 17q22 and 22q13, the gene loci which code the alpha chain of type I collagen. The diagnosis is made histologically. Differentiation from atypical dermatofibroma and dermatomyofibroma, as well as from malignant fibrous histiocytoma, whose prognosis is usually much less favorable, can be improved by immunostaining for CD 34 and Factor XIIIa. The extent of the tumors can be estimated by CT and more precisely with MRI. All these techniques fail to detect the fine tumor fascicles extending into the adjacent connective tissue and fat. Surgery is the therapy of choice for DFSP. The locally infiltrative growth pattern features clinically inapparent extensions which often extend for long distances in a horizontal direction. These tumor extensions are best detected by uninterrupted histological check of all margins, including the base (3-D-histology), with paraffin sections. Re-excision of tumor-positive areas until tumor-free margins are obtained ("histographic surgery") insures a high cure rate (97%) while preserving normal tissue.

Dermatofibrosarcoma↗

Truncation of activated leukocyte cell adhesion molecule: a gateway to melanoma metastasis.

Progression of human cutaneous primary melanoma is, among others, accompanied by de novo expression of activated leukocyte cell adhesion molecule (ALCAM/CD166) and enhanced activity of proteolytic cascades in the invasive, vertical growth phase (VGP) of lesions. The homophilic cell adhesion function of wild-type ALCAM mediates homotypic clustering of melanoma cells and would, thus, antagonize cell release from the primary tumor, an early prerequisite for metastasis. Stable transfection of a transmembrane, amino-terminally truncated ALCAM (DeltaN-ALCAM) into metastatic cells diminished cell clustering mediated by wild-type ALCAM. We have addressed the biological effects of DeltaN-ALCAM on tumorigenicity and found that the relief of cell clustering constraints promoted motility in vitro and the transition from expansive tumor growth to tissue invasion in reconstructed skin in culture. In a transplant tumor model, the changes were reflected in reduced subcutaneous tumor growth and in accelerated, spontaneous lung metastasis. These data indicate that the intact cell adhesion function of ALCAM may both favor primary tumor growth and represent a rate-limiting step for tissue invasion from VGP melanoma. ALCAM induction could, thus, provide an attractive target for proteolysis as a part of a more complex cellular program that couples growth and migration and facilitates dissemination.

Activated-Leukocyte Cell Adhesion Molecule↗

Polymorphisms of the BRAF gene predispose males to malignant melanoma.

The incidence of malignant melanoma has rapidly increased in recent years. Evidence points to the role of inheritance in melanoma development, but specific genetic risk factors are not well understood. Recent reports indicate a high prevalence of somatic mutations of the BRAF gene in melanomas and melanocytic nevi. Here we report that germ-line single nucleotide polymorphisms (SNPs) in BRAF are significantly associated with melanoma in German males, but not females. At-risk haplotypes of BRAF are shown. Based upon their frequencies, we estimate that BRAF could account for a proportion attributable risk of developing melanoma of 4% in the German population. The causal variant has yet to be determined. The burden of disease associated with this variant is greater than that associated with the major melanoma susceptibility locus CDKN2A, which has an estimated attributable risk of less than 1%.

Journal Article↗

The prevalence of human papillomavirus genotypes in nonmelanoma skin cancers of nonimmunosuppressed individuals identifies high-risk genital types as possible risk factors.

Nonmelanoma skin cancer is the most commonly diagnosed malignant disease in Caucasians. Known risk factors include fair skin, sun exposure, male gender, advancing age, and the presence of solar keratosis. No viral risk factors have been established thus far. To examine the association between nonmelanoma skin cancer and infection with human papilloma virus (HPV) types, we performed a retrospective study in which skin biopsies were collected from 496 nonimmunosuppressed patients attending dermatologic clinics during a defined period and for whom a biopsy or resection of a tumor was indicated for medical reasons. A total of 390 patients with histologically confirmed diagnosis of warts (n = 209), solar keratosis or Bowen's disease (n = 91), squamous cell carcinoma (n = 72), or basal cell carcinoma (n = 18), as well as 106 control patients with normal skin was analyzed for infection with HPV and, if positive, HPV typed by sequencing. Logistic regression was performed to separately investigate association of certain HPV types with the occurrence of warts, precancerous lesions, and skin cancer compared with normal skin. For all three histological groups, both crude risk and risk adjusted for age, sex, and sun exposure were calculated. HPV DNA was detected in only 4.7% of controls, in 90.9% of benign warts, in 60.4% of precancerous lesions, in 59.7% of squamous cell carcinoma, and in 27.8% of basal cell carcinoma, which demonstrates that viral infection is specifically linked to skin disorders. The distribution of viral types found is distinctly different between warts and precancers or cancers, supporting an etiologic role of specific HPV types. This is supported by statistical analysis, where after adjusting for age, gender, and sun exposure, the odds ratio for nonmelanoma skin cancer in patients who were DNA positive for the high-risk mucosal HPV types, 16, 31, 35, and 51 was 59 (95% confidence interval, 5.4-645) with normal skin as controls. These findings suggest that persistent infections of the skin with high risk genital HPV types recently identified as significant risk factors for cervical cancer may also represent a risk factor for nonmelanoma skin cancer in a nonimmunosuppressed population.

Adolescent↗

Exclusion of BRAFV599E as a melanoma susceptibility mutation.

Very recently, BRAF mutations were found in about 2/3 of malignant melanomas and at lower frequencies in other human cancers. The BRAF gene codes for a protein in the mitogen-activated protein kinase (MAPK) pathway. All mutations identified to date are within the kinase domain, with a single missense mutation (V599E) accounting for 80%. We investigated the hypothesis that this common somatic BRAF mutation (V599E) would contribute to melanoma predisposition in familial and polygenic malignant melanoma if occurring as a germ-line mutation. We performed comprehensive mutational screening of exon 15 of BRAF using DHPLC (denaturing high-performance liquid chromatography) and DNA sequencing techniques. No V599E mutation could be detected in 172 melanoma patients comprising 46 familial cases, 21 multiple melanoma patients and 106 cases with at least one first-degree relative suffering from other cancers. We therefore conclude that the common somatic BRAF mutation V599E does not contribute to polygenic and familial melanoma predisposition.

Alleles↗

Diagnostic value and prognostic significance of protein S-100beta, melanoma-inhibitory activity, and tyrosinase/MART-1 reverse transcription-polymerase chain reaction in the follow-up of high-risk melanoma patients.

BACKGROUND: Cutaneous melanoma is the most aggressive form of skin carcinoma in humans, frequently with a rapid progression of disease. To detect early developing metastasis, laboratory tests to determine levels of lactate dehydrogenase (LDH) and alkaline phosphatase (AP) form part of the regular follow-up, but often cannot discover recurrent disease at a sufficiently early stage. METHODS: To evaluate the diagnostic accuracy of protein S-100beta (S-100beta), melanoma-inhibitory activity (MIA), LDH, AP, and tyrosinase/MART-1 reverse transcription-polymerase chain reaction (RT-PCR), the authors included 296 consecutive AJCC Stage II or III clinically disease-free melanoma patients. Follow-up examinations were performed every 3 months and blood samples were drawn to determine the levels of these tumor markers. RESULTS: Metastasis occurred in 41 of the 296 patients during a median follow-up period of 19 months (range, 1-33 months). The sensitivity to detect new metastases was 29% for protein S-100beta, 22% for MIA, 2% for LDH, 17% for AP, and 24% for RT-PCR. The diagnostic accuracy was best for MIA (86%) and S-100beta (84%), whereas AP (79%), LDH (77%), and RT-PCR (72%) demonstrated lower values. Elevated values of S-100beta and MIA during follow-up examinations were associated with decreased survival rates in the further course of the disease, but pathologic findings of the other tumor markers showed no prognostic impact. CONCLUSIONS: To the authors' knowledge, the current study is the first comparison of the diagnostic accuracy of currently available tumor markers in the follow-up of high-risk melanoma patients. Protein S-100beta and MIA demonstrated a higher sensitivity, specificity, and diagnostic accuracy in the diagnosis of newly occurring metastasis compared with to the tumor markers AP, LDH, and RT-PCR diagnostics. Therefore, the tumor markers S-100beta and MIA may be useful in the follow-up of disease-free Stage II and III melanoma patients.

Adult↗

Continuous long-term monitoring of UV radiation in professional mountain guides reveals extremely high exposure.

Ultraviolet radiation (UVR) is estimated to be one of the most important risk factors for nonmelanoma and melanoma skin cancers. High occupational UV exposure is assumed to be associated with skin cancer. Mountain guides receive considerable UV doses due to altitude-related increase of UVR and reflection from snow- and ice-covered surfaces. The aim of our study was to assess the annual occupational UV exposure of mountain guides. Spore film test chambers containing spores of Bacillus subtilis (VioSpor) were used as UV dosimeters with a spectral sensitivity profile similar to erythema-weighted data calculated from spectroradiometric measurements. Nine mountain guide instructors carried dosimeters on the sides of their heads on a total of 1,406 working days during one year (July 1999-June 2000). Dosimeters were changed monthly. Measurements of 92 months could be evaluated (4-12 months/mountain guide). The mean individual monthly UV exposure was 107 standard erythema doses (SED) (median 71 SED; range 10-505 SED). The mean annual cumulative UV exposure was 1,097 SED (median 1,273 SED; range 312-1,770 SED) per mountain guide. The mean UV dose per day (4-10 hr) was 6.6 SED (median 5.7 SED; range 0.6-24.2 SED). This is the second study of continuous annual UV dosimetry in a cohort of outdoor workers. Our study showed that it is not sufficient to interpolate annual UV exposure from a few days' measurements. Only long-term dosimetry can give reliable yearly information of UVR load. Median daily UV exposure exceeded limits for UV radiation (e.g., ACGIH effective dose 30 J/m(2) per 8 hr period corresponding to 1.08 SED/day) 6-fold; maximal exposure exceeded these limits 23-fold. These extremely high exposure values are suggestive for an increased risk of skin cancer and thorough epidemiologic studies in the collectives of professional and recreational mountaineering are required.

Germany↗

Moderate sun exposure and nevus counts in parents are associated with development of melanocytic nevi in childhood: a risk factor study in 1,812 kindergarten children.

BACKGROUND: Melanocytic nevi have been identified as the most important risk factor for cutaneous melanoma. Sun exposure, sunburns, and light pigmentation have been found to be associated with their development in childhood. To the authors' knowledge, nevus proneness of parents and the exact type of ultraviolet (UV) exposure have not yet been investigated in this context. The authors' objective was to determine independent risk factors and their impact for nevus development in childhood. METHODS: The current study was conducted by two university departments of dermatology in 49 public nursery schools in Stuttgart, Germany and in 38 public nursery schools in Bochum, Germany. The cross-sectional study included 1,812 children aged 2-7 years and their parents. Total body nevus counts in children, assessment of pigmentary features, and nevus counts on the arms of parents were performed. Parents underwent a standardized interview concerning national origin and lifestyle features, as well as habits and magnitude of sun exposure of children. Analysis was performed by multivariate linear regression analysis and by multiple logistic regression analysis. RESULTS: The number of nevi was found to steadily increase with age from a median of 3 at age 2 years to 19 at age 7 years (P < 0.0001). High numbers of nevi in children were associated with the number of weeks on sunny holidays, outdoor activities at home, skin type, facial freckling, ethnicity of parents, and the number of nevi on the arms of parents. Previously experienced sunburns failed significance (P = 0.0620). CONCLUSIONS: The authors found a strong association between nevus development in children and the number of parental moles, which most likely points to an inherited factor. Moderate sun exposure such as outdoor activities during a German summer without sunburns seemed to be sufficient for induction of melanocytic nevi. The authors believe that these findings will have direct impact on concepts for preventive strategies.

Adult↗

Prospective evaluation of a follow-up schedule in cutaneous melanoma patients: recommendations for an effective follow-up strategy.

PURPOSE: To prospectively examine and evaluate the results of follow-up procedures in a large cohort of cutaneous melanoma patients. PATIENTS AND METHODS: This was a prospective study in 2,008 consecutive patients with stage I to IV cutaneous melanoma from 1996 to 1998 on the yield of stage-appropriate follow-up examinations according to the German guidelines. Documentation of patient and follow-up data comprised patient demography, primary tumor specifics, and any clinical and technical examinations performed. The detection of metastasis was classified as early or late, and the means of their detection and the resulting overall survival probabilities were examined. RESULTS: A total of 3,800 clinical examinations and 12,398 imaging techniques were documented. Sixty-two second primary melanomas in 46 patients and 233 disease recurrences in 112 patients were detected during this time. In stage I to III disease, physical examination was responsible for the discovery of 50% of all recurrences. In the primary tumor stages, 21% of all recurrences were discovered by lymph node sonography, with the majority being classified as early detection. Forty-eight percent of the recurrences were classified as early detection, and these patients had a significant benefit of overall survival probability. CONCLUSION: The results of our study suggest that an elaborated follow-up schedule in cutaneous melanoma is suitable for the early detection of second primary melanomas and early recurrences. The intensity of clinical and technical examinations can be reduced during follow-up of patients in the primary tumor stages and may be intensified in locoregional disease. Recommendations for an effective follow-up strategy are outlined.

Cohort Studies↗

Tumor lymphangiogenesis: a novel prognostic indicator for cutaneous melanoma metastasis and survival.

Malignant melanomas of the skin are distinguished by their propensity for early metastatic spread via lymphatic vessels to regional lymph nodes, and lymph node metastasis is a major determinant for the staging and clinical management of melanoma. However, the importance of tumor-induced lymphangiogenesis for lymphatic melanoma spread has remained unclear. We investigated whether tumor lymphangiogenesis occurs in human malignant melanomas of the skin and whether the extent of tumor lymphangiogenesis may be related to the risk for lymph node metastasis and to patient survival, using double immunostains for the novel lymphatic endothelial marker LYVE-1 and for the panvascular marker CD31. Tumor samples were obtained from clinically and histologically closely matched cases of primary melanomas with early lymph node metastasis (n = 18) and from nonmetastatic melanomas (n = 19). Hot spots of proliferating intratumoral and peritumoral lymphatic vessels were detected in a large number of melanomas. The incidence of intratumoral lymphatics was significantly higher in metastatic melanomas and correlated with poor disease-free survival. Metastatic melanomas had significantly more and larger tumor-associated lymphatic vessels, and a relative lymphatic vessel area of >1.5% was significantly associated with poor disease-free and overall survival. In contrast, no differences in the density of tumor-associated blood vessels were found. Vascular endothelial growth factor and vascular endothelial growth factor-C expression was equally detected in a minority of cases in both groups. Our results reveal tumor lymphangiogenesis as a novel prognostic indicator for the risk of lymph node metastasis in cutaneous melanoma.

Adult↗

Palliative therapy of disseminated malignant melanoma: a systematic review of 41 randomised clinical trials.

We undertook a systematic review of 41 randomised studies in disseminated melanoma, identified by a comprehensive search. We aimed to investigate rates of response to various treatment modalities and the outcome for the patients. We analysed seven studies that compared polychemotherapy with single-agent dacarbazine, six that compared different chemotherapeutic schedules with each other, five on the addition of tamoxifen to a reference therapy, and six that included non-specific immunostimulators. In 17 studies, the addition of interferon alfa, interleukin 2, or both, to a reference therapy was investigated, including trials with biochemotherapy. Many trials had small sample sizes and did not report a power analysis; not all were analysed by intention to treat. Although some treatment regimens, especially polychemotherapeutic schedules, seem to increase response rates, none of the treatment schedules was proven to prolong overall survival. Patients with disseminated melanoma should be treated with well-tolerated drug regimens, such as single-agent treatments or in combination with interferon alfa. Systemic treatments should preferably be investigated in randomised trials so that the potential benefits of new treatment concepts can be thoroughly examined.

Antineoplastic Agents↗

Fibroblast growth factor-2 but not Mel-CAM and/or beta3 integrin promotes progression of melanocytes to melanoma.

A variety of melanoma-associated antigens have been identified that mediate adhesion, growth, proteolysis, and modulation of immune response. However, the mechanisms by which human normal melanocytes become malignant are not clearly understood. Among the most consistent observations is the up-regulation of fibroblast growth factor-2 (FGF-2) and of the adhesion molecules beta3 integrin and Mel-CAM during melanoma progression. To evaluate the potential role of FGF-2, beta3 integrin and Mel-CAM in melanoma development we overexpressed FGF-2, beta3 integrin and Mel-CAM in normal human melanocytes using replication-deficient adenoviruses as a gene delivery vehicle. Fibroblast growth factor-2 overexpressing melanocytes in monolayer culture displayed cytological atypia. Furthermore, in human skin reconstructs where the physiological milieu is recreated in vitro, FGF-2-overexpressing melanocytes exhibited marked proliferation, upwards migration, cluster formation and type IV collagen expression within the epidermal compartment, simulating early radial growth phase melanoma. In contrast, overexpression of beta3 integrin and/or Mel-CAM in melanocytes did not affect their biological behaviour in human skin reconstructs. The described results of the current and previous studies emphasise the key role of FGF-2 in melanoma development and progression, underscoring the promise of FGF-2 as a target for therapy.

Adenoviridae↗

Acquired melanocytic nevi as risk factor for melanoma development. A comprehensive review of epidemiological data.

Acquired melanocytic nevi (MN) in Caucasian populations are important markers for the risk of melanoma development. The total number of MN on the whole body is the most important independent risk factor for melanoma and the risk of melanoma development increases almost linearly with rising numbers of MN. Additionally, the presence of atypical MN and of actinic lentigines are likewise independent risk factors for melanoma. Atypical mole syndrome should be defined by the presence of many acquired MN and a threshold number of atypical MN. Acquired MN develops mainly during childhood and adolescence in the first two decades of life. The number of acquired nevi seems to be related to hereditary factors and nevus-prone families exist. The amount of sun exposure is the most important environmental risk factor for nevus development, particularly in early childhood. Interestingly, sunburns may play a role in nevus development, but seem not to be required, and even moderate sun exposure promotes the process. Therefore, preventive measures for nevus and melanoma development should target young children and adolescents.

Dysplastic Nevus Syndrome↗

Direct effects on proliferation, antigen expression and melanin synthesis of cultured normal human melanocytes in response to UVB and UVA light.

BACKGROUND/PURPOSE: Ultraviolet (UV) radiation; induces a variety of responses in the skin, including tanning and inflammation, and may also act as a carcinogen. As epidermal melanocytes are seen as the major targets of UV light, the present study was conducted to evaluate the direct effects of UVA and UVB irradiation on melanocytes in vitro. METHODS: Normal human epidermal melanocytes (NHM) were exposed on 3 consecutive days to UVA (0.072-7.2 J/cm2) and UVB (7.2-48 mJ/cm2), respectively, and changes of morphology, cell number, melanin synthesis and antigen expression (APAAP technique) were determined 5 days after the first exposure. RESULTS: UVA radiation caused only minimal effects on NHM by slightly inducing expression of the activation marker HMB-45 and decreasing expression of the proliferation marker Ki-67. No changes of morphology, cell number or melanin synthesis were detectable with any of the applied doses. On the other hand, UVB radiation significantly induced dendrite formation and decreased the number of NHM in a dose-dependent manner (74% of the controls at 7.2 mJ/cm2, 64% at 14.4 mJ/cm2 and 28% at 36 mJ/cm2). Significant induction of the activation marker HMB-45 was found in parallel to decreased expression of the differentiation marker K.1.2.58. UVB doses >or=9.6 mJ/cm2 also resulted in significant downregulation of the proliferation marker Ki-67, confirming the data of the cell counts, and melanin content was increased in NHM (20% over the controls, P<0.01) after applying 7.2 mJ/cm2 UVB. CONCLUSION: Our results may suggest that the effect of UVB radiation in skin is due to direct activation of melanocytes, whereas skin tanning caused by UVA is mediated rather in an indirect way.

Antibodies, Monoclonal↗

"Functional" surgery in subungual melanoma.

BACKGROUND: Subungual melanomas represent approximately 2% to 3% of cutaneous melanomas in White populations. Complete or partial amputation proximal to the distal interphalangeal joint of the digits has been suggested. Recently, we introduced for acral melanomas, similar to lentigo maligna melanoma, limited excision and complete histology of excisional margins (three-dimensional histology). OBJECTIVE: To evaluate the prognostic relevance of clinical parameters and different surgical management in patients with subungual melanoma. STUDY DESIGN: From 1980 to 1999, subungual melanoma was diagnosed in 62 of 3,960 stage I and II melanoma patients (1.6%) of the melanoma registry of the Department of Dermatology (University of Tuebingen). A retrospective comparative analysis of two treatment groups was performed: Thirty-one patients had an amputation in or proximal to the distal interphalangeal joint (median follow-up of 55 months), and 31 patients had "functional" surgery with local excision of the tumor and only partial resection of the distal phalanx (median follow-up of 54 months). RESULTS: In the univariate analysis, the level of invasion (P=0.0059), ulceration (P=0.0024), and tumor thickness (P=0.0004) were significant prognostic factors for recurrence-free survival but not for survival. In a multivariate analysis, only lower tumor thickness and a reduced level of amputation were independent significant prognostic parameters for recurrence-free survival (P=0.035 and P=0.0069). Patients with an amputation in or proximal to the distal interphalangeal joint did not fare better than patients with less radical "functional" surgery. CONCLUSION: Limited excision with partial resection of the distal phalanx only and three-dimensional histology to assure tumor-free resection margins give better cosmetic and functional results and do not negatively affect the prognosis of patients with subungual melanoma.

Adult↗

[Psychosocial burden and subjective experience of melanoma patients in the ambulant follow-up].

INTRODUCTION: The ambulant follow-up is established for early detection of metastases thus improving the survival probability of tumor patients. In spite of the safety aimed at, follow-up also puts a burden on tumor patients and has effects on their quality of life. AIM: To investigate within the scope of follow-up, to collect data on the psychosocial burden on melanoma patients in relation to the predictors (medical factors, psychological variables, sociodemographic data) in order to define a "burden-risk patient". METHOD: From June to December 1997, 615 ambulant melanoma patients were questioned with the aid of the Hornheide questionnaire and the German version of the Hospital Anxiety and Depression Scale (HADS-D). RESULTS: The leading predictors for a psychosocial burden were found to be fear and depression, as well as tumor thickness, metastases, year of operation, sex, age, and marital status/household. With the aid of these results, a burden-risk patient could be defined: female sex, age between 40 and 59 years, divorced or widowed, separately living, with a tumor thickness of more than 4 mm, first diagnosis less than 3 years ago and prevailing metastases. This risk patient had also a high probability of having significant fear and depression values. CONCLUSION: The use of the Hornheide questionnaire for identifying the psychosocial burden is suitable to collect the individual burdens of the patients in particular and within a short period. In the same way, the needs of the patients can be met in particular, and thus his/her quality of life can be increased.

Adult↗

Modified ABC-point list of dermoscopy: A simplified and highly accurate dermoscopic algorithm for the diagnosis of cutaneous melanocytic lesions.

BACKGROUND: The use of dermoscopy (epiluminescence microscopy, surface microscopy, dermatoscopy) improves clinical diagnostic sensitivity by 10% to 27%, particularly achieved by different algorithms or scores. OBJECTIVE: We sought to develop a simplified and highly accurate dermoscopic-point list for cutaneous melanocytic lesions. METHOD: We studied consecutive patients with suspicious melanocytic lesions, which were excised and histopathologically examined at our institution. On the basis of the ABCD rule of Stolz, Menzies score, and the modified ABCD rule of Kittler, a simplified ABC-point list was developed. Simple points were given for the following: asymmetry of outer shape (A) or differential structures inside the lesion in at least 1 axis ((A)); the abrupt cutoff of network at the border in at least one quarter of circumference (B); 3 or more colors (C); 3 or more differential structures (D); or noticed change (evolution) in the last 3 months (E). Using 20-fold magnification of computer dermoscopy, the sensitivity, specificity, and diagnostic accuracy were examined in 269 cutaneous melanocytic lesions. Of these, 84 (31.2%) were cutaneous melanomas. Also, the sensitivity, specificity, and diagnostic accuracy were investigated with a 7-point checklist and the 7 features for melanoma. RESULTS: With the ABC-point list for the diagnosis of cutaneous melanoma, sensitivity was 90.5%, specificity was 87%, and diagnostic accuracy was 88.1%, confirmed by cross-validation. The ABCD rule resulted in 90.5%, 72.4%, and 78.1%; Menzies score in 95.2%, 77.8%, and 83.3%; 7-point checklist in 90.5%, 87%, and 88.1%; and 7 features for melanoma in 94%, 74.6%, and 80.7%, respectively, CONCLUSIONS: The ABC-point list is simpler than the already established algorithms. Despite its simplicity, a high sensitivity, specificity, and diagnostic accuracy was achieved. This simplified approach in dermoscopic diagnostics may contribute to further spread and enable to learn and use this method more easily.

Algorithms↗

Detection of dermcidin-derived peptides in sweat by ProteinChip technology.

Recently, a novel antimicrobial peptide DCD-1, derived from the Dermcidin (DCD) gene and secreted by sweat glands, has been described by Schittek et al. [Nat. Immunol. 2 (2001) 1133.]. Here we describe the application of the surface-enhanced laser desorption/ionisation (SELDI) technology for the detection of DCD-1 and other dermcidin-derived peptides directly from microlitre amounts of human sweat. The advantages of the technique are as follows: (a) it can be carried out with ease and rapidity; (b) multiple samples can be processed simultaneously; (c) prior purification is not required; and (d) only a limited sample volume is necessary for both protein profiling and semiquantitation. Profiling of human sweat from various donors revealed that in addition to DCD-1, other DCD-derived peptide species were also present in significant quantities. Four of five identified peptides were DCD-1 related, while the fifth corresponded to a portion of the DCD protein outside the DCD-1 core. This provides clues as to how the novel protein is processed to its active form, though further work remains to elucidate this fully. Thus, we have demonstrated the applicability of such technology to the detection of DCD-1 and for the protein profiling of sweat in general. Such studies could reveal valuable new biomarkers for diagnosis and treatment of skin and sweat gland disorders.

Amino Acid Sequence↗