Melanoma: Stolz W

Garbe C, Hauschild A, Volkenandt M, Schadendorf D, Stolz W, Reinhold U, Kortmann RD, Kettelhack C, Frerich B, Keilholz U, Dummer R, Sebastian G, Tilgen W, Schuler G, Mackensen A, Kaufmann R. · University Department of Dermatology, Tübingen, Germany. · Melanoma Res. · Pubmed #18337653 No free full text.

Abstract: Systemic medical treatment of melanoma is administered in the adjuvant and palliative setting. Adjuvant therapy may be considered in patients with primary melanoma with more than 1.5 mm tumor thickness and with regional node metastasis. Presently no indication for systemic adjuvant chemotherapy or for adjuvant therapy with nonspecific immune-stimulatory agents outside controlled studies is seen. Interferon-alpha is the first substance in the adjuvant therapy of melanoma, which has shown to present a significant advantage to the patients in some prospective randomized studies. Good arguments for using adjuvant interferon-alpha therapy in high-risk melanoma patients exist. Both high-dose and low-dose interferon-alpha show promise. The major indications for systemic chemotherapy and chemoimmunotherapy are inoperable recurrent tumors, inoperable regional metastases and distant metastases (stage IV). As treatment in such situations is primarily palliative, the effect of any regimen on the quality of life must be carefully weighed. As a first line treatment, single agent therapy is recommended, as polychemotherapy or biochemotherapy did not show significant advantages for prolongation of survival; hence they are more toxic. An urgent need for development of new treatment modalities is necessary and general principles of experimental immunotherapy are outlined.

Garbe C, Hauschild A, Volkenandt M, Schadendorf D, Stolz W, Reinhold U, Kortmann RD, Kettelhack C, Frerich B, Keilholz U, Dummer R, Sebastian G, Tilgen W, Schuler G, Mackensen A, Kaufmann R. · University Department of Dermatology, Tübingen, Germany. · Melanoma Res. · Pubmed #18227710 No free full text.

Abstract: The primary treatment of a melanoma is surgical excision. An excisional biopsy is preferred, and safety margins of 1 cm for tumor thickness up to 2 mm and 2 cm for higher tumor thickness should be applied either at primary excision or in a two-step procedure. When dealing with facial, acral or anogenital melanomas, micrographic control of the surgical margins may be preferable to allow reduced safety margins and conservation of tissue. The sentinel lymph node biopsy should be performed in patients whose primary melanoma is thicker than 1.0 mm and this operation should be performed in centers where both the operative and nuclear medicine teams are experienced. In clinically identified lymph node metastases, radical lymph node dissection is considered standard therapy. If distant metastases involve just one internal organ and operative removal is feasible, then surgery should be seen as therapy of choice. Radiation therapy for the primary treatment of melanoma is indicated only in those cases in which surgery is impossible or not reasonable. In regional lymph nodes, radiation therapy is usually recommended when excision is not complete (R1 resection) or if the nodes are inoperable. In distant metastases, radiation therapy is particularly indicated in bone metastases, brain metastases and soft tissue metastases.

Stoecker WV, Stolz W. · No affiliation provided · Arch Dermatol. · Pubmed #18794468 No free full text.

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Roesch A, Burgdorf W, Stolz W, Landthaler M, Vogt T. · Department of Dermatology, University of Regensburg, Franz-Josef-Strauss-Allee 11, D-93053 Regensburg, Germany. · Eur J Dermatol. · Pubmed #17101467 links to  free full text

Abstract: The sequential progression model for melanocytic tumours from common nevus to malignant melanoma was proposed by Clark almost 30 years ago. The "dysplastic nevus" has frequently been considered a logical offspring of this concept and as a direct precursor of melanoma, analogous to the epithelial dysplasia-carcinoma sequence. Despite the use of modern molecular methods, there is no consensus as to if the dysplastic nevus represents a true precursor lesion of melanoma, a separate distinct type of nevus, or a diagnostic dilemma. Currently, the concept of melanocytic dysplasia remains subject to confusing definitions at all levels of the diagnostic process, i.e. clinical appearance, dermatohistopathology, and molecular biology. In this review, we collect evidence that nevi fulfilling Clark and Elder's classic histological criteria mostly represent "endpoints" of nevocytic evolution, whereas a minority of "dysplastic nevi" represent true melanoma precursors. The unsolved dilemma is that neither clinical, histopathological nor molecular criteria exist to make a distinction between dysplastic nevi and early melanomas. Our analysis of the current knowledge on dysplastic nevi shows that dermatoscopy remains the only quantifiable, easily applicable and reproducible diagnostic tool to approach the problem. Due to a "quantum leap" in optical resolution, objective scores can be established, e.g. the total dermatoscopy score (TDS) according to the ABCD rule, and documentation of changes over time are possible by digital image storage devices. Although dermatoscopy does not solve the dilemma of discriminating early, basically feature-less melanomas from dysplastic nevi, and it does not prove that dysplastic nevus is a distinct entity, it helps make melanocytic tumours with unclear malignant potential a manageable disease.

Garbe C, Hauschild A, Volkenandt M, Schadendorf D, Stolz W, Kortmann RD, Kettelhack C, Frerich B, Keilholz U, Dummer R, Sebastian G, Tilgen W, Schuler G, Mackensen A, Kaufmann R. · Universitäts-Hautklinik Tübingen. · J Dtsch Dermatol Ges. · Pubmed #16638065 No free full text.

This publication has no abstract.

Schiffner R, Schiffner-Rohe J, Landthaler M, Stolz W. · Clinic of Dermatology and Allergology, Hospital Munich Schwabing, 80804, Munich, Germany. · Br J Dermatol. · Pubmed #12890198 No free full text.

Abstract: BACKGROUND: Digital dermoscopy for the follow-up of melanocytic naevi (MN) is becoming more common in dermatological private practice. OBJECTIVES: To evaluate the clinical outcome, including the patient's compliance, in a long-term follow-up of single MN. METHODS: Criteria for the selection of MN for follow-up: clinically suspicious without dermoscopically atypical features, or typical for the patient. Clinical outcome measures: number of detected malignant melanomas (MM) and/or atypical MN; quantity, quality, and differences in morphological changes between 'low-risk' patients (no MM in history and < 50 MN) and 'high-risk' patients (MM in history and/or > 50 MN). Compliance: the number of patients who joined a recommended follow-up scheme. RESULTS: No MM was found in 145 consecutive patients (mean age 28 years, 54% female) during a 4-year period (median follow-up per patient: 24 months; ranging 4-45; at least three visits). In five patients (3%), seven histologically proven atypical MN were shown on whole body examination at sites other than those documented. A total of 1968 images in 177 'low-risk' and 95 'high-risk' MN were analysed: 37% (n = 65) of 'low-risk' and 32% (n = 30) of 'high-risk' MN showed dermoscopic changes (difference not statistically significant), none were suspicious for MM. Compliance, evaluated within a separate database of 303 consecutive patients (mean age 32 years, 52% female) over a 6-month period, was only 46%, although recall letters were used. CONCLUSIONS: (i) In our setting of daily routines in dermatological private practices long-term follow-up of a single MN seems not to be helpful for the detection of MM. (ii) A whole body examination must be done at each visit. (iii) The clinician's experience of the type and number of possible morphological changes in MN is crucial in order to avoid unnecessary excisions. (iv) The patient's compliance might be an important problem. (v) Cost-effectiveness has yet to be analysed.

Stolz W, Semmelmayer U, Johow K, Burgdorf WH. · Department of Dermatology, Hospital Munich-Schwabing, Munich, Germany. · Semin Cutan Med Surg. · Pubmed #12773010 No free full text.

Abstract: There has been a dramatic increase in the incidence of malignant melanoma in most parts of the world. Because the tumor thickness is the most important prognostic factor for the prognosis of the malignant melanoma, the early detection of thin melanomas is essential. Dermatoscopy allows the physician to discriminate between melanocytic and nonmelanocytic lesions with high diagnostic accuracy and to detect initial malignant melanomas. We review the principles of dermatoscopy and the differential diagnosis of pigmented skin lesions. Before using the ABCD rule of dermatoscopy to classify melanocytic lesions into benign, suspicious, or malignant, the distinction between melanocytic and nonmelanocytic lesions is necessary. An essential prerequisite for the usefulness of this technique is adequate training.

Argenziano G, Soyer HP, Chimenti S, Talamini R, Corona R, Sera F, Binder M, Cerroni L, De Rosa G, Ferrara G, Hofmann-Wellenhof R, Landthaler M, Menzies SW, Pehamberger H, Piccolo D, Rabinovitz HS, Schiffner R, Staibano S, Stolz W, Bartenjev I, Blum A, Braun R, Cabo H, Carli P, De Giorgi V, Fleming MG, Grichnik JM, Grin CM, Halpern AC, Johr R, Katz B, Kenet RO, Kittler H, Kreusch J, Malvehy J, Mazzocchetti G, Oliviero M, Ozdemir F, Peris K, Perotti R, Perusquia A, Pizzichetta MA, Puig S, Rao B, Rubegni P, Saida T, Scalvenzi M, Seidenari S, Stanganelli I, Tanaka M, Westerhoff K, Wolf IH, Braun-Falco O, Kerl H, Nishikawa T, Wolff K, Kopf AW. · Department of Dermatology, Second University of Naples, Italy. · J Am Acad Dermatol. · Pubmed #12734496 No free full text.

Abstract: BACKGROUND: There is a need for better standardization of the dermoscopic terminology in assessing pigmented skin lesions. OBJECTIVE: The virtual Consensus Net Meeting on Dermoscopy was organized to investigate reproducibility and validity of the various features and diagnostic algorithms. METHODS: Dermoscopic images of 108 lesions were evaluated via the Internet by 40 experienced dermoscopists using a 2-step diagnostic procedure. The first-step algorithm distinguished melanocytic versus nonmelanocytic lesions. The second step in the diagnostic procedure used 4 algorithms (pattern analysis, ABCD rule, Menzies method, and 7-point checklist) to distinguish melanoma versus benign melanocytic lesions. kappa Values, log odds ratios, sensitivity, specificity, and positive likelihood ratios were estimated for all diagnostic algorithms and dermoscopic features. RESULTS: Interobserver agreement was fair to good for all diagnostic methods, but it was poor for the majority of dermoscopic criteria. Intraobserver agreement was good to excellent for all algorithms and features considered. Pattern analysis allowed the best diagnostic performance (positive likelihood ratio: 5.1), whereas alternative algorithms revealed comparable sensitivity but less specificity. Interobserver agreement on management decisions made by dermoscopy was fairly good (mean kappa value: 0.53). CONCLUSION: The virtual Consensus Net Meeting on Dermoscopy represents a valid tool for better standardization of the dermoscopic terminology and, moreover, opens up a new territory for diagnosing and managing pigmented skin lesions.

Stolz W, Schiffner R, Burgdorf WH. · Department of Dermatology, University of Regensburg, Regensburg, Germany. · Clin Dermatol. · Pubmed #12074867 No free full text.

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Cognetta AB, Stolz W, Katz B, Tullos J, Gossain S. · Dermatology Associates, Tallahassee, Florida, USA. · Dermatol Clin. · Pubmed #11556239 No free full text.

Abstract: Lentigo maligna and LMM require different dermatoscopic criteria for evaluation. The ease and accessibility of examining these lesions with dermatoscopy coupled with the clinical pathologic correlation afforded by the biopsy techniques discussed allow the practitioner to become proficient and prescient with the use of dermatoscopy. The criteria mentioned here are relatively new but are present and detectable in most cases of LM and LMM. The fact that there is some overlap among pigmented actinic keratosis, squamous cell carcinoma in situ, and lichenoid keratosis lesions should not detract or deter the physician from using dermatoscopy. Clinically, these lesions also usually will be equivocal and will require close clinical scrutiny and biopsies. If given the choice of using skin surface microscopy for one class of lesion only, one might well choose LM lesions because of their otherwise subtle nature and the clues that can be unlocked with oil immersion, illumination, and magnification, along with knowledge of these new criteria.

Hauschild A, Garbe C, Stolz W, Ellwanger U, Seiter S, Dummer R, Ugurel S, Sebastian G, Nashan D, Linse R, Achtelik W, Mohr P, Kaufmann R, Fey M, Ulrich J, Tilgen W. · Department of Dermatology, Christian-Albrechts-University, Kiel. · Br J Cancer. · Pubmed #11308250 links to  free full text

Abstract: In several phase II-trials encouraging tumour responses rates in advanced metastatic melanoma (stage IV; AJCC-classification) have been reported for the application of biochemotherapy containing interleukin 2. This study was designed to compare the efficacy of therapy with dacarbazine (DTIC) and interferon alpha (IFN-alpha) only to that of therapy with DTIC and IFN-alpha with the addition of interleukin 2 (IL-2) in terms of the overall survival time and rate of objective remissions and to provide an elaborated toxicity profile for both types of therapy. 290 patients were randomized to receive either DTIC (850 mg/m(2)every 28 days) plus IFN-alpha2a/b (3 MIU/m(2), twice on day 1, once daily from days 2 to 5; 5 MIU/m(2)3 times a week from week 2 to 4) with or without IL-2 (4.5 MIU/m(2)for 3 hours i.v. on day 3; 9.0 MIU/m(2) i.v. day 3/4; 4.5 MIU/m(2) s.c. days 4 to 7). The treatment plan required at least 2 treatment cycles (8 weeks of therapy) for every patient. Of 290 randomized patients 281 were eligible for an intention-to-treat analysis. There was no difference in terms of survival time from treatment onset between the two arms (median 11.0 months each). In 273 patients treated according to protocol tumour response was assessable. The response rates did not differ between both arms (P = 0.87) with 18.0% objective responses (9.7% PR; 8.3% CR) for DTIC plus IFN-alpha as compared to 16.1% (8.8% PR; 7.3% CR) for DTIC, IFN-alpha and IL-2. Treatment cessation due to adverse reactions was significantly more common in patients receiving IL-2 (13.9%) than in patients receiving DTIC/IFN-alpha only (5.6%). In conclusion, there was neither a difference in survival time nor in tumour response rates when IL-2, applied according to the combined intravenous and subcutaneous schedule used for this study, was added to DTIC and IFN-alpha. However, toxicity was increased in melanoma patients treated with IL-2. Further phase III trials with continuous infusion and higher dosages must be performed before any final conclusions can be drawn on the potential usefulness of IL-2 in biochemotherapy of advanced melanoma.

Garbe C, Schadendorf D, Stolz W, Volkenandt M, Reinhold U, Kortmann RD, Kettelhack C, Frerich B, Keilholz U, Dummer R, Sebastian G, Tilgen W, Schuler G, Mackensen A, Kaufmann R, Hauschild A. · Sektion Dermatologische Onkologie, Universitäts-Hautklinik, Liebermeister Strasse 25, D-72076 Tübingen, Germany. · J Dtsch Dermatol Ges. · Pubmed #18801142 No free full text.

This publication has no abstract.

Garbe C, Hauschild A, Volkenandt M, Schadendorf D, Stolz W, Reinhold U, Kortmann RD, Kettelhack C, Frerich B, Keilholz U, Dummer R, Sebastian G, Tilgen W, Schuler G, Mackensen A, Kaufmann R. · University Department of Dermatology, Tübingen, Germany. · Melanoma Res. · Pubmed #17992123 No free full text.

Abstract: Melanoma is a malignant tumor that arises from melanocytic cells and primarily involves the skin. The most important exogenous etiological factor is exposure to ultraviolet irradiation. Diagnosis of melanoma is based primarily on its clinical features, and the A-B-C-D rule is useful in identifying pigmented lesions, which are suspicious for melanoma (Asymmetry, Border irregular, Color inhomogeneous and Diameter more than 5 mm). Dermoscopy is very helpful in clarifying the differential diagnosis of pigmented lesions. About 90% of melanomas are diagnosed as primary tumors without any evidence for metastasis. The tumor-specific 10-year survival for all such tumors is about 75-85%. The most important prognostic factors for primary melanoma without metastases are vertical tumor thickness (Breslow depth) as measured on the histological specimen, presence of histopathologically recognized ulceration, invasion level (Clark level) and identification of micrometastases in the regional lymph nodes via sentinel lymph node biopsy. The current tumor node metastasis classification for the staging of primary melanoma is based on these factors. Melanomas can metastasize either by the lymphatic or by the hematogenous route. About two-thirds of metastases are originally confined to the drainage area of regional lymph nodes. A regional metastasis can appear as satellite metastases up to 2 cm from the primary tumor, as intransit metastases in the skin between the site of the primary tumor and the first lymph node and as regional lymph node metastases. In the stage of regional metastasis, the differentiation between micrometastasis and macrometastasis and the number of lymph nodes involved are crucial. As soon as distant metastasis develops, prognosis depends on the site of the metastasis and on the lactate dehydrogenase levels in the blood. The frequency and extent of follow-up examinations is based on the initial tumor parameters. In thin primary melanomas up to 1-mm tumor thickness, clinical examinations at 6-month intervals are sufficient and in thicker primary melanomas, at 3-month intervals. Lymph node sonography as well as determination of the tumor marker protein S100beta are recommended. Additionally, in the stage of regional metastasis, whole body imaging should be performed every 6 months; in the stage of distant metastasis, surveillance has to be scheduled individually.

Vogl A, Sartorius U, Vogt T, Roesch A, Landthaler M, Stolz W, Becker B. · Department of Dermatology, University of Regensburg, D-93042 Regensburg, Germany. · J Invest Dermatol. · Pubmed #15675960 links to  free full text

Abstract: Vaccination protocols based on autologous tumor material often require in vitro culturing of tumor cells to obtain enough cellular material for the production of the vaccine. Cancer cells and particularily melanoma cells are known for their genomic instability. Therefore, it can be assumed that melanoma cells acquire genomic changes and thereby changes in the transcriptome during in vitro culturing. This may lead to a shift of epitopes expressed on the tumor cells. We analyzed the transcriptome of in vitro cultured melanoma cells prepared from melanoma metastases. Comparing the gene expression changes between the tumors and their offspring cell lines, we demonstrate that with increasing passage numbers, gene expression changes increase drastically.

Schiffner R, Perusquia AM, Stolz W. · Clinic of Dermatology and Allergology, Hospital München Schwabing, Kölner Platz 1, D-80804 Munich, Germany. · Br J Dermatol. · Pubmed #15541091 No free full text.

Abstract: We report a 64-year-old man with a pigmented lesion on his forehead, initially thought to be actinic lentigo. At follow-up 1 year later the lesion had increased in size and showed new areas of pigmentation. Dermoscopic observation and biopsy led to a diagnosis of lentigo maligna and the lesion was excised. The dermoscopic features indicative of early growth of lentigo maligna are identified and discussed.

Cabo H, Stolz W. · Hospital de Clinicas, University of Buenos Aires, Buenos Aires, Argentina. · Dermatol Surg. · Pubmed #15209804 No free full text.

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Durnick A, Stolz W, Landthaler M, Vogt T. · Department of Dermatology, University of Regensburg, Regensburg, Germany. · Dermatol Surg. · Pubmed #15099332 No free full text.

Abstract: BACKGROUND: We observed two young women with skin types II to III according to Fitzpatrick's classification who developed pigmented macules in the face that were histologically diagnosed as lentigo maligna melanomas. OBJECTIVE: The objective of this study was to examine lentigo maligna melanoma in young adults. METHODS: According to private photographs of one of those patients a precursor lesion was clinically apparent as early as in her 26th year. Ten years later, the diagnosis of a lentigo maligna melanoma was made. The other patient was diagnosed with lentigo maligna at the age of 37. After excision, a relapse occurred in her 39th year. At this time histopathology revealed an early invasive lentigo maligna melanoma. RESULTS: These case reports demonstrate that the diagnosis of both lentigo maligna and lentigo maligna melanoma cannot be dismissed because of young age or well-tanning skin types. CONCLUSION: We conclude that owing to changes in social behavior and sporting activities with high short-term ultraviolet exposures, one must be aware of the possibility of an unusual early onset of lentigo maligna and lentigo maligna melanoma already in the third and fourth decade of life. Furthermore, our observations support the effectiveness of dermatoscopy in diagnosing ambiguous pigmented skin lesions in sun-exposed skin.

Becker B, Roesch A, Hafner C, Stolz W, Dugas M, Landthaler M, Vogt T. · Department of Dermatology, University of Regensburg, Regensburg, Germany. · J Invest Dermatol. · Pubmed #15009717 links to  free full text

Abstract: Gene expression profiling by cDNA array analysis in melanoma is hampered by the need for large amounts of RNA to prepare reliable probes for array hybridization. On the other hand, for ex vivo analysis of malignant cells from melanocytic tumors laser pressure catapulting is an essential prerequisite to obtain noncontaminated melanocytic preparations; however, laser pressure catapulting prepared material provides only nanogram amounts of RNA. In this study we present an approach to overcome these limitations by combining laser pressure catapulting and real-time polymerase chain reaction based SMART cDNA amplification technology. Reproducible and reliable hybridization patterns from about 500 laser pressure catapulting prepared cell equivalents from 22 cases of melanocytic tumors were generated using array analysis. Univariate analysis revealed significant differences of the expression pattern of melanocytic nevi, melanomas, and melanoma metastases. Multivariate analysis with four genes being the best univariate discriminative features (tyrosinase related protein 2, translation initiation factor 2 gamma, ubiquitine conjugating enzyme E2I and one expressed sequence tag) allowed clustering of nevi, melanomas, and melanoma metastases with an accuracy of 82%. Data validation was performed by additional quantitative reverse transcription-polymerase chain reaction (TaqMan-reverse transcription-polymerase chain reaction). Taken together, this study shows, that (1) array analysis is feasible on tumors with rather low cell numbers, and (2) differences in expression profiles allow discrimination between benign and malignant lesions. Expression patterns of marker genes defined in unequivocal histopathologic entities may improve the diagnostic and prognostic assessment of difficult melanocytic lesions, which is still the hardest problem in dermatopathology.

Becker B, Multhoff G, Farkas B, Wild PJ, Landthaler M, Stolz W, Vogt T. · Department of Dermatology, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany. · Exp Dermatol. · Pubmed #15009113 No free full text.

Abstract: The heat-shock protein Hsp90 has been shown to be essential for the functional integrity of the telomerase complex. The telomerase activity is enhanced in melanoma and stabilizes the chromosomal integrity in proliferating cells. Furthermore, overexpression of Hsp90 induces silencing of point mutations in transcription factors which, otherwise, would result in a loss-of-function phenotype. In melanocytic lesions there is a higher risk of mutations caused by the enhanced proliferation in melanocytic cells. By analyzing microdissected melanocytic tumors by semiquantitative PCR, we demonstrate an overexpression of Hsp90 mRNA in malignant melanomas (10/14) and in melanoma metastases (6/6) as well as in melanoma cell lines (9/9) when compared with melanocytic nevi (2/9). These results could be confirmed on protein level by immunohistochemistry. While melanocytic nevi show discrete Hsp90 expression only in a minor fraction (2/9), malignant melanomas and metastases show a positive Hsp90 immunohistochemistry in the majority of cases; (7/9) and (13/14), respectively. In addition, by analyzing melanoma metastases by flow cytometry we show that Hsp90 is expressed on the surface of tumor cells (7/8). From these data we conclude that Hsp90 is present in advanced malignant melanomas and may have a stabilizing effect on the cellular functions in proliferating cells of melanocytic lesions and could thereby be a prerequisite for the tumor progression. As Hsp90 is expressed on the cell surface, it might also be a potential immunorelevant target structure for immunotherapy of melanoma.

Rumpler G, Becker B, Hafner C, McClelland M, Stolz W, Landthaler M, Schmitt R, Bosserhoff A, Vogt T. · Department of Dermatology, University of Regensburg, Germany. · Exp Dermatol. · Pubmed #14714555 No free full text.

Abstract: Currently, the scale and consistency of changes of gene expression profiles in models of melanoma progression are largely unknown. Therefore, we investigated siblings of cell lines or malignant melanomas (MM), which have been selected by nude mouse passages for (a). increased tumorigenicity (local ECM-independent growth), (b). metastatic potential, or (c). selected for increase invasiveness using the Boyden chamber. cDNA array analysis surveying more than 27.000 transcripts per cell line showed that 1.5-2.8% of all detectable transcripts were consistently differentially regulated during selection process in those models. Using array analysis, we identified 33 individual transcripts that exhibited significant differential hybridization paralleling the increased aggressiveness of the selected progeny. Because some of those genes could play a significant functional role in the progression of MM, we additionally proved their regulative pattern using Northern blotting. Among others, progressive overexpression of osteonectin/SPARC, a angiogenesis, was found in the selected offspring from all three experimental models and may therefore be considered as a potential marker for aggressive MM as well a promising therapeutic target. We further show that the selection of MM cells for increased ECM-independent local growth was accompanied by overexpresssion of macrophage migration inhibiting factor (MIF), an important modulator of both cell cycle progression and angiogenesis, and cathepsin Z, a novel member of the family of matrix degrading proteinases.

Klebl FH, Gelbmann CM, Lammert I, Bogenrieder T, Stolz W, Schölmerich J, Schlottmann K. · Klinik und Poliklinik für Innere Medizin I, Klinikum der Universität, Regensburg. · Med Klin (Munich). · Pubmed #14685681 No free full text.

Abstract: BACKGROUND AND PURPOSE: Early detection of metastases of malignant melanoma has therapeutic implications. The aim of this study was to evaluate palpation and ultrasound examination in the diagnostics of lymph node metastases in locally advanced melanoma. PATIENTS AND METHODS: 83 patients suffering from melanoma (Clark level IV or V) were examined for lymph node metastases by palpation and sonography. Findings were compared to histopathologic results after lymph node extirpation if available or the findings at the next follow-up visit. RESULTS: Lymph node metastases were confirmed histopathologically in 14 patients at the first study visit, in three others at the control visit. Sensitivity, specificity, positive and negative predictive values of palpation for the detection of metastases or suspicious nodes with increasing volume at follow-up in this population were 65%, 81%, 48%, and 89%, and of ultrasound 100%, 66%, 45%, and 100%, respectively. CONCLUSION: Sonography of lymph nodes should be included as a standard procedure in the detection of metastases of locally advanced malignant melanoma.

Roesch A, Vogt T, Stolz W, Dugas M, Landthaler M, Becker B. · Department of Dermatology, University of Regensburg, Franz-Josef-Strauss-Allee 11, D-93053 Regensburg, Germany. · Melanoma Res. · Pubmed #14512792 No free full text.

Abstract: Genes that determine the invasive capacity of the invasive front of malignant melanomas (MM) have not yet been systematically investigated in vivo. Therefore, we combined laser pressure catapulting (LPC) microdissection with cDNA microarray technology (DermArray, Research Genetics, representing about 5700 genes) to systematically analyse differences in gene expression profiles between the invasive margin and the tumour centre in nine cases of vertical growth phase MM. Signal-to-noise statistical algorithms combined with hierarchical clustering were performed to determine class-separating genes. The gene encoding phosphoenolpyruvate carboxykinase 1 (PEPCK), the Homo sapiens gene similar to Saccharomyces cerevisiae SSM4 (TEB4), the gene encoding ribosomal protein L19, the Homo sapiens gene similar to the Aspergillus nidulans SudD (a suppressor of the bimD6 homologue), the gene encoding the interleukin-3 receptor alpha subunit, the gene encoding the inositol 1,4,5-triphosphate 3-kinase isoenzyme, and three anonymous expressed sequence tags were identified as class-separating genes. These genes significantly discriminate between the invasive front and the tumour centre. Using this set of genes, 15 out of 18 LPC-dissected MM regions could be grouped correctly. We conclude that the candidate genes identified could spark further research on MM progression and may provide novel prognostic parameters.

Schiffner R, Wilde O, Schiffner-Rohe J, Stolz W. · Clinic of Dermatology and Allergology Hospital Munich-Schwabing, Kölner Platz 1, D-80804 München, Germany. · Eur J Dermatol. · Pubmed #12804992 links to  free full text

Abstract: Clear proceedings in detection of malignant melanoma and monitoring of melanocytic nevi (MN) have been achieved by dermoscopy in recent years: sensitivity to 95% is possible for experts. Does patients' confidence in methods for detection of malignant melanoma most important for adherence in follow-up reflect this diagnostic power? A self-administered survey was performed in 210 consecutive patients at 13 private dermatological practices and the department of Dermatology of the University of Regensburg. Confidence was assessed by a 5-step ordinal scale ranging from 1 to 5 (higher values indicate higher confidence) and willingness-to-pay (wtp) as health-economic instrument for naked-eye inspection (NEI), handheld dermoscopy (HHD), digital dermoscopy (DD), and teledermoscopy (TD); additional, wtp for a hypothetical method promising 100% accuracy. Data of 143 patients (response rate 69.5%; mean age 37 years, 58% female) could be analysed. Mean confidence was 1.9 0.9 for NEI, 2.8 0.9 for HHD, 4.5 0.7 for DD, and 4.7 0.5 for TD. Mean wtp per examination was 0.64% 1.1 of monthly income for NEI, 1.1% 1.9 for HHD, 2.8% 3.3 for DD, 3.1% 4.6 for TD, and 5.0% 7.8 for hypothetical method. Differences between methods were statistically significant. Compared to the hypothetical method, NEI achieved only 14.9%, HHD 24.8%, DD 58.4%, and TD 60% of maximum confidence. This study was performed without any influence on routine information for patients. Results therefore represent patients' actual knowledge of dermoscopical methods in daily dermatological practices. Patients' confidence was highest for TD, HHD was clearly underestimated. Willingness-to-pay in HHD, DD, and TD was at least 40% below a hypothetical method promising 100% accuracy. Better information about diagnostic accuracy of methods available is necessary to increase patients' knowledge and confidence.

Coras B, Glaessl A, Kinateder J, Klövekorn W, Braun R, Lepski U, Landthaler M, Stolz W. · Department of Dermatology, University of Regensburg, Germany. · Curr Probl Dermatol. · Pubmed #12472014 No free full text.

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Westphal G, Burgemeister R, Friedemann G, Wellmann A, Wernert N, Wollscheid V, Becker B, Vogt T, Knüchel R, Stolz W, Schütze K. · P.A.L.M. Microlaser Technologies AG, 82347 Bernried, Germany. · Methods Enzymol. · Pubmed #12418190 No free full text.

This publication has no abstract.