Melanoma Res 2006 Jun; 16(3): 245-248 (Read article online)

Oʼneill PA, Butt M, Eswar CV, Gillis P, Marshall E

Uveal melanoma is relatively uncommon accounting for fewer than 5% of all melanoma cases. Localized tumours are curable by local therapy but a significant percentage of patients go on to have a relapse with metastatic disease. Uncertainty remains concerning the level of activity of dacarbazine in uveal melanoma as opposed to that in the cutaneous form. Recently, a possible role for treosulfan in uveal disease has been reported. A phase II study was therefore undertaken to assess the objective response rate of the combination of dacarbazine and treosulfan in previously untreated patients with metastatic uveal melanoma. All patients received dacarbazine 850 mg/m and treosulfan 8 g/m every 21 days up to a maximum of six cycles. Fifteen patients enrolled in the study. As expected, the major toxicities were haematological (particularly thrombocytopaenia) but the treatment was generally well tolerated. No responses were seen; however, disease stabilization was achieved in two patients. Median progression free survival from the start of chemotherapy was 12 weeks and median overall survival was 30 weeks. This study, using the combination of dacarbazine and treosulfan, while well tolerated, did not confirm earlier reports suggesting treosulfan is active in uveal melanoma.

J Neurooncol 2006 May; 78(1): 71-80 (Read article online)

Parney IF, Chang LJ, Farr-Jones MA, Hao C, Smylie M, Petruk KC

OBJECTIVE: Malignant glioblastomas and melanomas continue to have a dismal prognosis despite advances in conventional therapy. This has led to investigations of novel treatment strategies including immunogene therapy. We report a pilot clinical trial of combined B7-2 and GM-CSF immunogene therapy for gliomas and melanomas and discuss technical hurdles encountered. METHODS: Patients with recurrent malignant gliomas or medically refractory melanomas were vaccinated with irradiated autologous tumor cells transduced with B7-2 and GM-CSF genes using a retroviral vector. Patients were monitored for toxicity, inflammatory/immune reactions, and clinical status. RESULTS: Vaccine preparation was attempted from 116 malignant glioma and 32 melanoma specimens. Adequate vaccines could only be prepared for five glioblastoma and three melanoma patients. Six patients (three recurrent glioblastomas and three melanomas) were actually vaccinated. Minor toxicities included flu-like symptoms (3/6), injection site erythema (4/6), and asymptomatic elevations in liver enzymes (3/6). Most patients showed evidence of an inflammatory response but specific anti-tumor immunity was not demonstrated. All six patients have died, although three patients with minimal residual disease at treatment had prolonged recurrence-free intervals after vaccination. CONCLUSIONS: Combined B7-2 and GM-CSF immunogene therapy for glioblastomas and melanomas using autologous tumor cells has many technical pitfalls hindering large scale application and evaluation. As a result, this pilot study was too limited to draw meaningful conclusions regarding safety or anti-tumor immunity. While immunotherapy has been promising in pre-clinical studies, alternate strategies will be required to bring these benefits to patients.

Environ Health 2006 May 22; 5(1): 13 (Read article online)

Prince MM, Hein MJ, Ruder AM, Waters MA, Laber PA, Whelan EA

ABSTRACT: BACKGROUND: The National Institute for Occupational Safety and Health previously reported mortality for a cohort of workers considered highly exposed to polychlorinated biphenyls (PCBs) between 1939 and 1977 at two electrical capacitor manufacturing plants. The current study updated vital status, examined liver and rectal cancer mortality previously reported in excess in this cohort and evaluated mortality from non-Hodgkin's lymphoma (NHL) and cancers of the stomach, intestine, breast, prostate, skin (melanoma) and brain reported to be in excess in other cohort and case-control studies of PCB-exposed persons. METHODS: Mortality was updated through 1998 for 2572 workers. Age-, gender-, race- and calendar year-adjusted standardized mortality ratios (SMRs) and 95% confidence intervals (CI) were calculated using U.S., state and county referent rates. SMRs using U.S. referent rates are reported. Duration of employment was used as a surrogate for exposure. RESULTS: Consistent with the previous follow-up, mortality from biliary passage, liver and gall bladder cancer was significantly elevated (11 deaths, SMR 2.11, CI 1.05 - 3.77), but mortality from rectal cancer was not (6 deaths, SMR 1.47, CI 0.54 - 3.21). Among women, mortality from intestinal cancer (24 deaths, SMR 1.89, CI 1.21 - 2.82) and other diseases of the nervous system and sense organs a category that includes Parkinson's disease and amyotrophic lateral sclerosis (15 deaths, SMR 2.07, CI 1.16 - 3.42) were elevated. Mortality was elevated for myeloma (7 deaths, SMR 2.11, CI 0.84 - 4.34), particularly among workers employed 10 years or more (5 deaths, SMR 2.80, CI 0.91 - 6.54). No linear associations between mortality and duration of employment were observed for the cancers of interest. CONCLUSIONS: This update found that the earlier reported excess in this cohort for biliary, liver and gall bladder cancer persisted with longer follow-up. Excess mortality for intestinal cancer among women was elevated across categories of duration of employment; myeloma mortality was highest among those working 10 years or more. The small numbers of deaths from liver and intestinal cancers, myeloma and nervous system diseases coupled with the lack of an exposure-response relationship with duration of employment preclude drawing definitive conclusions regarding PCB exposure and these causes of death.

Biosci Biotechnol Biochem 2006 May; 70(5): 1218-26 (Read article online)

Kim GY, Lee JY, Lee JO, Ryu CH, Choi BT, Jeong YK, Lee KW, Jeong SC, Choi YH

Many polysaccharides isolated from mushroom are considered to be biological response modifiers and have been shown to enhance various immune responses in vivo and in vitro. We demonstrate that a novel polysaccharide-protein complex (PPC) extracted from Phellinus linteus was a potent immunomodulator. PPC had a molecular weight of approximately 73 kDa. It was composed of five different monosaccharides, predominantly D-glucose and D-mannose, in the molar ratio of 3:2, the main amino acid being aspartic acid. PPC had a unique mode of immunostimulation with regard to its cell-type specificity. PPC was found to markedly increase the proliferation of B cells, but not T cells. Although PPC and lipopolysaccharide (LPS) had a similar mode of action in B cells, they were differentiated by the fact that PPC-induced cellular activation was not inhibited by polymyxin B (PB), a specific inhibitor of LPS. PPC increased the cytokine production and nitric oxide (NO) from macrophages. PPC also enhanced the lytic death of NO-sensitive tumor cells, B16 melanoma, through the production of NO. In addition, PPC up-regulated the natural killer (NK) cell-mediated killing of tumor cells, YAC-1 lymphoma in vitro. These results suggest that PPC stimulated the tumoricidal activities of macrophages and NK cells, and induced the proliferation of B cells in vitro. This process may be the mechanism by which PPC produced its therapeutic effects.

Medicina (B Aires) 2006; 66(2): 144-6 (Read article online)

Denninghoff V, Falco J, Curutchet HP, Elsner B

Survival at 5 years of patients with localized primary malignant melanoma is about 80%, compared with a 35% survival in case of lymph nodes involvement. Sentinel lymph node(s) from 45 subjects with diagnosis of malignant melanoma stage I or II was/were studied with hematoxylin-eosin (HE), immunohistochemistry (IHC) and molecular biology (MB) techniques. The population was divided into three groups: HE-/IHC+/MB+, where 67% patients died; HE-/IHC-/MB+, where 57% died; and HE-/IHC-/MB-, where 100% of the patients are alive, with no lymphadenectomy and a median follow-up of 60 months. Those subjects who showed negativity with all the three methods had a null recurrence rate. Data herein obtained suggest a new molecular oncological staging, which would allow the selection of patients with submicroscopic metastases for a complete treatment. Moreover, several patients with no lymph node metastases should not undergo lymphadenectomies, and overtreatment could therefore be avoided.

Ann Surg Oncol 2006 May 23; (Read article online)

Bastiaannet E, Hoekstra OS, Oyen WJ, Jager PL, Wobbes T, Hoekstra HJ

BACKGROUND: The incidence of malignant melanoma has increased. Identification of additional prognostic factors may allow the development of individualized strategies. This multivariate analysis was undertaken to evaluate the potential role of the standard uptake value (SUV) in predicting disease-free and overall survival in melanoma patients with lymph node metastases. METHODS: All melanoma patients with palpable lymph node metastases who where referred for a fluorodeoxyglucose positron emission tomography scan were eligible. The SUV in the lymph node metastasis was calculated. Data were analyzed (Kaplan-Meier), and differences in cumulative survival and the disease-free rate were assessed (log-rank test). Univariate and multivariate analyses (Cox proportional hazard model) were performed to determine independent prognostic factors. RESULTS: There was no statistical difference in survival for the 38 patients with a high or low SUV(mean) (P = .11). However, a significant difference was found in disease-free survival (P = .03). Ulceration of the primary melanoma (P = .023) was an independent predictor of survival. For the disease-free survival, multivariate Cox regression showed adjuvant radiation (P = .001), localization of the primary melanoma (P = .017), and a high SUV(mean) (P = .009) as independent prognostic factors. CONCLUSIONS: Disease-free survival of melanoma patients was prolonged in those with a low SUV(mean) value (P = .03) in their lymph node metastasis, as compared with those with a high SUV(mean). However, this difference was not found for overall survival. In multivariate analysis, high SUV(mean) was an independent prognostic factor (P = .009) for disease-free survival. Prospective research should determine whether patients with a high FDG uptake in melanoma lymph node metastases could benefit from adjuvant radiation treatment or chemotherapy.

Melanoma Res 2006 Jun; 16(3): 223-34 (Read article online)

Büscher K, Hahn S, Hofmann M, Trefzer U, Ozel M, Sterry W, Löwer J, Löwer R, Kurth R, Denner J

The human endogenous retrovirus-K encodes two potential tumor proteins, Rec and Np9. Rec is related to the Rev protein of HIV-1 and has been shown to be associated with tumor development in nude mice. Having shown the expression of human endogenous retrovirus-K in human melanomas and melanoma cell lines, tools were developed to allow the expression of the transmembrane envelope, Rec and Np9 mRNA and proteins to be studied in more detail. The expression of spliced env, rec and np9 was investigated by reverse transcriptase-polymerase chain reaction using a set of primers developed to discriminate between full-length and spliced mRNA. Env-specific, Rec-specific and Np9-specific antisera were produced, characterized and used to study protein expression in melanomas and melanoma cell lines by immunohistochemistry, immunofluorescence and Western blot analyses. Existence of human endogenous retrovirus-K Rec and Np9-specific antibodies in the sera of melanoma patients were analyzed by Western blot of immunofluorescence studies. The expression of both spliced env and rec mRNA was detected in 39% of the melanomas and in 40% of the melanoma cell lines and np9 mRNA was detected in 29 and 21%, respectively. In normal neonatal melanocytes, spliced rec mRNA was detected in the absence of spliced env mRNA. Using antisera specific for Rec and Np9, Rec protein was found in 14% of the melanomas but Np9 in none. In addition, cell surface expression of the putatively immunosuppressive transmembrane envelope protein and release of virus particles were shown. Antibodies specific for neither Rec nor Np9 were detected. The transmembrane envelope protein, Rec and Np9 proteins are expressed in melanoma cells with a pattern similar to that seen in teratocarcinoma cell lines. Additional experiments are needed to determine their involvement, if any, in cell proliferation and tumor progression.

J Plast Reconstr Aesthet Surg 2006; 59(6): 644-52 (Read article online)

Hamdi M, Van Landuyt K, de Frene B, Roche N, Blondeel P, Monstrey S

INTRODUCTION: Anatomy and classification of intercostal perforator flaps in addition to our experience with will be demonstrated for different indications. MATERIAL AND METHODS: The intercostal vessels form an arcade between the aorta and the internal mammary vessels. Different pedicled perforator flaps can be raised on this neurovascular bundle to cover defects on the trunk. They are classified as following: dorsal intercostal artery perforator flap (DICAP); lateral intercostal artery perforator (LICAP); and anterior intercostal artery perforator (AICAP) flap. RESULTS: Between 2001 and 2004, 20 pedicled (ICAP) flaps were harvested in 16 patients. The indications were: immediate partial breast reconstruction in eight patients who had a quadrantectomy for breast cancer; midline back and sternal defects in three patients who had radical excisions for a dermatofibrosarcoma or malignant melanoma; and autologous breast augmentation (four bilateral and one unilateral flap) in five post-bariatric-surgery patients. The average flap dimension was 18x8cm(2) (range 8x5-24x12cm(2)). There were two DICAP flaps, two (AICAP) flaps and 16 (LICAP) flaps. All but two flaps were based on one perforator. Mean harvesting time was 45min for a single flap. Bilateral breast augmentation with LICAP flap necessitated longer operative time (range 2-3h) depending whether it was combined or not with mastopoexy. Complete flaps survival was obtained. All donor sites were closed primarily. CONCLUSION: The (ICAP) flaps provide valuable options in breast surgery; and for challenging defects on the trunk without sacrifice of the underlying muscle.

Melanoma Res 2006 Jun; 16(3): 207-11 (Read article online)

Shellman YG, Makela M, Norris DA

Degradation of matrix proteins that constitute the dermal-epidermal junction and dermis by proteolytic enzymes is an essential step of melanoma invasion and metastasis, and this is primarily achieved by the matrix metalloproteinases. In this report, using zymography, we compared the basal secretion levels of active matrix metalloproteinase-2 and matrix metalloproteinase-9 to levels in response to various extracellular matrix proteins, cytokines, and growth factors in normal human melanocyte cells and melanoma cell lines from different stages of neoplastic progression. Basal matrix metalloproteinase-9 activity was only detected in vertical growth phase and metastatic melanoma cell lines, suggesting that matrix metalloproteinase-9 is a candidate biomarker for identifying vertical growth phase and metastatic melanomas. Most melanoma cell lines and cultured normal melanocytes produced high levels of matrix metalloproteinase-2. In addition, both tumor necrosis factor-alpha and interleukin-1beta are strong inducers of active matrix metalloproteinase-9 in vertical growth phase melanoma cell lines, indicating a possible role of these cytokines in the switch from radial growth phase to vertical growth phase. We propose that these proinflammatory cytokines promote melanoma invasion in part through upregulating matrix metalloproteinase-9. Both these cytokines are released from keratinocytes in the epidermis by ultraviolet radiation. Thus, our study suggests that the microenvironment of melanoma cells is an important feature in melanoma progression, and ultraviolet-radiation-induced cytokines might promote the progression of melanoma through the release or activation of matrix metalloproteinases.

Melanoma Res 2006 Jun; 16(3): 201-6 (Read article online)

Zanetti R, Loria D, Rosso S

Since the early 1970s, a number of case reports have suggested that levodopa therapy for Parkinson's disease increases the risk of cutaneous malignant melanoma. As yet, no formal epidemiological study has been conducted to verify this hypothesis. To elucidate the relationship between levodopa and the risk of cutaneous malignant melanoma, a systematic literature search using computerized bibliographic databases was done. This review presents the case history evidence for and against the hypothesis of a causal association, and explores possible epidemiological, genetic, social, biochemical and toxicological factors that may increase the risk of melanoma in Parkinson's disease patients. All the case reports in the literature were considered. We concluded that (1) there is no epidemiological or experimental evidence of a causal role of levodopa in increasing the risk of melanoma incidence or progression; (2) there is good evidence of an excess risk of melanoma in patients with Parkinson's disease; (3) there is good evidence of a protective effect of tobacco smoking on the risk for Parkinson's disease; (4) there is good evidence of positive correlation between social class and melanoma risk; (5) the relationship between the risk of Parkinson's disease and the risk of melanoma may be due to a common genetic profile or it can be attributed to a confounding role of social class, associated with both melanoma and Parkinson's disease possibly through an inverse relationship with tobacco smoking.

Ann Surg Oncol 2006 May 22; (Read article online)

Mangas C, Hilari JM, Paradelo C, Rex J, Fernández-Figueras MT, Fraile M, Alastrue A, Ferrándiz C

BACKGROUND: We performed this study to evaluate the clinical effect of microscopic and submicroscopic metastases in sentinel lymph nodes (SLNs) from patients with early-stage melanoma. METHODS: Patients with confirmed cutaneous melanoma (American Joint Committee on Cancer stages I and II) underwent standard lymphoscintigraphy and SLN biopsy. Serial sections were divided between routine histopathology with hematoxylin and eosin plus immunohistochemistry for HMB-45 and molecular analysis by nested reverse transcriptase-polymerase chain reaction (RT-PCR) assay for tyrosinase (using beta-actin as a control). RESULTS: Of 180 patients analyzed (318 SLNs), 38 (21%) patients had positive SLN(s) by routine hematoxylin and eosin and immunohistochemistry (microscopic disease; group 1), and 142 (79%) had negative histological results. Analysis by RT-PCR detected tyrosinase in at least 1 SLN from 124 (69%) patients. Among patients with histologically negative SLN(s), tyrosinase was detected in 86 (48%) patients (submicroscopic disease; group 2), whereas 40 (22%) patients had negative results by both histology and RT-PCR (group 3). Sixteen (9%) patients had histologically negative SLNs and ambiguous RT-PCR results (group 4). Among 138 patients in the analysis of recurrence (mean follow-up, 45 months), only 18 patients had a recurrence: 11 (31%) of 35 in group 1, 5 (10%) of 51 in group 2, and 2 (5%) of 37 in group 3. No recurrences were seen in group 4. Only group 1 had a significantly shorter disease-free survival and overall survival compared with the other groups. CONCLUSIONS: After a long follow-up period, molecular upstaging by tyrosinase RT-PCR failed to detect a subgroup of patients with an increased probability of recurrence.

Melanoma Res 2006 Jun; 16(3): 213-222 (Read article online)

Sadej R, Spychala J, Skladanowski AC

Ecto-5'-nucleotidase is a GPI-anchored enzyme localized in cell membrane lipid rafts. Although it is highly expressed in many tumour cells, its specific function during tumorigenesis is unclear. We have found that, among different melanoma cells, upregulated expression of ecto-5'-nucleotidase is associated with a highly invasive phenotype. Analysis of other cell membrane proteins involved in melanoma adhesion and metastasis demonstrated that expression of alpha5, beta1, beta3-integrin subunits and CD44 was elevated gradually in accordance with increasing metastatic potential. Expression of alphav-integrin and caveolin-1 was seen mostly in cells derived from metastatic melanomas. Furthermore, in contrast to N-cadherin, which was unaltered in all lines, we could not detect E-cadherin in any cell type. Functional assays demonstrated that highly expressed ecto-5'-nucleotidase is a catalytically competent protein that is very sensitive to inhibition by concanavalin A. The interaction with concanavalin A also caused increased association of ecto-5'-nucleotidase-rich lipid rafts with much heavier cytoskeletal complexes as determined by density gradient centrifugation. A similar shift towards heavier cytoskeletal fractions also took place with other proteins coexpressed with ecto-5'-nucleotidase, such as alphav, alpha5, beta1 and beta3-integrins, caveolin-1 and CD44. As ConA-induced clustering may reflect the interactions of membrane proteins with extracellular matrix, we also analysed the effect of several extracellular matrix proteins on the in-situ activity of ecto-5'-nucleotidase in WM9 cells and found that tenascin C strongly inhibited ecto-5'-nucleotidase activity and adenosine generation from AMP. We also developed WM9 cells with reduced ecto-5'-nucleotidase expression and tested differences in cell adhesion on various extracellular matrix proteins. WM9 cells attached significantly weaker to tenascin C layer. These observations indicate that expression of ecto-5'-nucleotidase correlates with a number of metastasis-related markers and thus may have a function in this process. Furthermore, our data suggest that, in addition to generating adenosine, ecto-5'-nucleotidase may have independent roles in adhesion and interaction with extracellular matrix components in melanoma.

Eur J Nucl Med Mol Imaging 2006 May 16; (Read article online)

Płachcińska A, Mikołajczak R, Kozak J, Rzeszutek K, Kuśmierek J

PURPOSE: The aim of the study was to determine an optimal method for the evaluation of scintigrams obtained with (99m)Tc-EDDA/HYNIC-TOC for the purpose of differential diagnosis of solitary pulmonary nodules (SPNs) and to assess the diagnostic value of the method. METHODS: Eighty-five patients (48 males and 37 females, mean age 57 years, range 34-78 years) were enrolled in the study. Patients underwent (99m)Tc-EDDA/HYNIC-TOC scintigraphy for the purpose of differential diagnosis of SPNs (size between 1 and 4 cm). Images of all patients were evaluated visually in a prospective manner. RESULTS: Positive scintigraphic results were found in 37 out of 40 (93%) patients with malignant SPNs including 34 out of 35 (97%) patients with primary lung carcinoma. Two remaining false negative cases turned out to be metastatic lesions of malignant melanoma and leiomyosarcoma. Among 45 benign tumours, negative results were obtained in 31 cases (69%) and positive results in 14. The accuracy of the method was 80%. Analysis of the results of the visual assessment of scintigrams revealed a significantly higher frequency of false positive results among larger nodules (diameter at least 1.4 cm). Uptake of the tracer in those nodules was therefore assessed semi-quantitatively (using the tumour-to-background ratio), in expectation of an improvement in the low specificity of the visual method. The semi-quantitative assessment reduced the total number of false positive results in a subgroup of larger nodules from 13 to six, while preserving the high sensitivity of the method. CONCLUSION: The combination of visual analysis (for lesions smaller than 1.4 cm in diameter) and semi-quantitative assessment (for larger lesions) provided a high sensitivity of the method and significantly improved its specificity (84%) and accuracy (88%) in comparison with visual analysis (p<0.05).

Cancer Immunol Immunother 2006 May 23; (Read article online)

Zippelius A, Gati A, Bartnick T, Walton S, Odermatt B, Jaeger E, Dummer R, Urosevic M, Filonenko V, Osanai K, Moch H, Chen YT, Old LJ, Knuth A, Jaeger D

Expression pattern and immunogenicity are critical issues that define tumor antigens as diagnostic markers and potential targets for immunotherapy. The development of SEREX (serological analysis of recombinant expression libraries) has provided substantial progress in the identification of tumor antigens eliciting both cellular and humoral immune responses in cancer patients. By SEREX, we have previously identified RAB38/NY-MEL-1 as a melanocyte differentiation antigen that is highly expressed in normal melanocytes and melanoma tissues but not in other normal tissues or cancer types. In this study, we further demonstrate that RAB38/NY-MEL-1 is strongly immunogenic, leading to spontaneous antibody responses in a significant proportion of melanoma patients. The immune response occurs solely in malignant melanoma patients and was not detected in patients with other diseases, such as vitiligo, affecting melanocytes. Fine analysis of the spontaneous anti-RAB38/NY-MEL-1 antibody response reveals a polyclonal B cell recognition targeting various epitopes, although a dominant immunogenic region was preferentially recognized. Interestingly, our data indicate that this recognition is not rigid in the course of a patient's response, as the dominant epitope changes during the disease evolution. Implications for the understanding of spontaneous humoral immune responses are discussed.

Mol Cell Biochem 2006 May 23; (Read article online)

Ratha J, Majumdar KN, Mandal SK, Bera R, Sarkar C, Saha B, Mandal C, Saha KD, Bhadra R

Lipids, especially sphingolipids, are emerging as inducer of apoptosis in a wide range of immortal cells, potentiating their therapeutic application in cancer. In the present study, a sphingolipid rich lipid fraction (denoted here as ALL), isolated from an attenuated strain of Leishmania donovani promastigote, was tested for its tumoricidal activity taking melanoma, the dreaded form of skin cancer cells, as model. ALL was found to induce chromatin condensation, internucleosomal DNA fragmentation and phosphatidylserine externalization with enhanced cell population in sub-G1 region in both mouse and human melanoma systems, namely B16F10 and A375 respectively. These are the hallmarks of cells undergoing apoptosis. Further analysis demonstrated that ALL treated melanoma cells showed significant increase in ROS generation, mitochondrial membrane potential depolarization, release of cytochrome c, and caspase-3 activation, which are the events closely involved in apoptosis. These findings indicate that one or more bioactive sphingolipid(s)/ceramide(s) present in ALL could be the causative agent(s) for the induction of apoptosis in melanoma cells. Further studies are thus necessary to identify these specific bioactive sphingolipid(s)/ceramide(s) and to establish their mechanism of action, in order to explore their use as anticancer agents.

Melanoma Res 2006 Jun; 16(3): 235-43 (Read article online)

Kuźbicki L, Gajo B, Chwirot BW

Lysosome-associated membrane protein-1 is a protein with a significant content of beta1,6-branched N-glycans. It is thought that enhanced expression of lysosome-associated membrane protein-1 in tumour cells may promote invasion by influencing both adhesion to extracellular matrix and perhaps also binding to endothelial cells. The present study was aimed at examining levels of lysosome-associated membrane protein-1 in human melanomas and benign pigmented lesions to evaluate whether this protein might be considered a potential molecular marker of melanoma progression. The expression of lysosome-associated membrane protein-1 was for the first time determined immunohistochemically in formalin-fixed paraffin-embedded specimens comprising 42 primary cutaneous melanomas, 15 lymph node melanoma metastases (11 correlated with primary tumours), three melanoma recurrences (correlated with both primary and metastatic melanomas), 27 nevi and four epithelial tumours (two seborrhoeic keratoses and two basal cell carcinomas). Our results demonstrate that development and progression of melanoma are associated with changes of the lysosome-associated membrane protein-1 level. The expression was strongest in melanoma recurrences and lymph node metastases, weaker in primary cutaneous melanomas and not detectable in melanocytes of pigmented nevi. Nodular melanomas expressed lysosome-associated membrane protein-1 at higher level than superficially spreading melanomas.

Melanoma Res 2006 Jun; 16(3): 263-265 (Read article online)

Lejeune FJ, Monnier Y, Rüegg C

Experimental and clinical evidence indicates that non-steroidal anti-inflammatory drugs and cyclooxygenase-2 inhibitors may have anti-cancer activities. Here we report on a patient with a metastatic melanoma of the leg who experienced a complete and sustained regression of skin metastases upon continuous single treatment with the cyclooxygenase-2 inhibitor rofecoxib. Our observations indicate that the inhibition of cyclooxygenase-2 can lead to the regression of disseminated skin melanoma metastases, even after failure of chemotherapy.

Ann Surg Oncol 2006 May 22; (Read article online)

Ranieri JM, Wagner JD, Wenck S, Johnson CS, Coleman JJ

BACKGROUND: Sentinel lymph node biopsy (SLNB) is prognostically useful in patients with cutaneous melanoma with Breslow thickness >1 mm. The objective of this study was to determine whether sentinel node histology has similar prognostic importance in patients with thin melanomas (

Melanoma Res 2006 Jun; 16(3): 259-61 (Read article online)

Kurul S, Aykan F, Tas F

Penile involvement has been implicated as a metastatic site in several tumors; approximately 300 cases have been reported. Of these, only two cases showed cutaneous melanoma as the primary site. Our patient presented with a painless mass on the penile shaft together with other distant metastases. A magnetic resonance image demonstrated two sites of deposit in the subcutaneous tissue on the radix penis, and fine needle aspiration cytology of the mass confirmed the presence of melanoma cells. The patient died of systemic disease without any further treatment for penile involvement. This unusual involvement is presented with a review of the related literature.

Eur J Dermatol 2006 May 1; 16(3): 276-280 (Read article online)

Top H, Aygit AC, Bas S, Yalcin O

Spitzoid melanoma is a rare variant of melanoma. It has morphological features similar to those of Spitz's nevus. In this study, the histologic and immunohistochemical features of both Spitzoid melanoma and Spitz's nevus are emphasized. We report two cases of melanoma with spitzoid features occurring in the extremities of 9 and 8-year-old girls. Histologically both lesions had typical features of Spitzoid melanoma. We conclude that the differential diagnosis of Spitzoid melanoma and Spitz's nevus is at times problematic in childhood, in that distant metastasis may be the only diagnostic criteria for some cases to be distinguished from Spitz's nevus if strict criteria are followed. Spitzoid melanoma must be treated as other types of melanoma.