Pigment Cell & Melanoma Research[JOURNAL]
Sun
155 papers
Structural asymmetry as a dermatoscopic indicator of malignant melanoma--a latent class analysis of sensitivity and classification errors.
Lorentzen HF, Weismann K, Larsen FG
Melanoma Res · 2001 Oct · PMID 11595887 · Publisher ↗
Asymmetry of pigmented skin lesions is an important indicator of possible malignant melanoma and contributes substantially to the diagnosis of melanoma in the dermatoscopic ABCD rule for melanocytic lesions and other alg...
Asymmetry of pigmented skin lesions is an important indicator of possible malignant melanoma and contributes substantially to the diagnosis of melanoma in the dermatoscopic ABCD rule for melanocytic lesions and other algorithms. However, it may be observer dependent. Dermatoscopic asymmetry cannot be assessed objectively and no golden standard of asymmetry diagnosis exists. The aim of this study was to assess the sensitivity of axis (a-) symmetry using latent class analysis. We analysed ratings from four experts in dermatoscopy of 232 pigmented lesions by latent class analysis (LCA). Possible ratings were 'no asymmetry', 'asymmetry in one axis' and 'asymmetry in two axes'. A subset of melanocytic lesions (blue naevi excluded) was analysed. Based on LCA, the asymmetry of the singular lesion was determined. The sensitivity of 'no asymmetry' was 40-77%, 40-70% for one-axis asymmetry, and 77-92% for two-axes asymmetry. Overestimation of asymmetry was more common than underestimation. Melanomas were significantly more asymmetric than pigmented naevi, atypical naevi and papillomas, but not basal cell cancers. Analysis of the melanocytic subset gave similar results. The median asymmetry of malignant melanomas (1.67, interquartile range 1.81-1.99) was higher than for melanocytic naevi. In conclusion, asymmetry and symmetry are important criteria for diagnosing or excluding malignant melanoma using the dermatoscopic ABCD rule, risk stratification and other diagnostic rules. Using LCA, we minimized observer dependence in the assessment of axis (a-) symmetry. LCA, besides conceptualizing the diagnostic process, enables the assignment of lesions to their true diagnostic class.
Epidemiology of digital epiluminescence microscopy features of acquired melanocytic naevi.
Stanganelli I, Bucchi L
Melanoma Res · 2001 Oct · PMID 11595885 · Publisher ↗
This study addressed the independent association of past and recent sun exposure indicators and other host factors with the prevalence of major digital epiluminescence microscopy (D-ELM) features such as the pigment netw...
This study addressed the independent association of past and recent sun exposure indicators and other host factors with the prevalence of major digital epiluminescence microscopy (D-ELM) features such as the pigment network (PN), brown globules (BGs), and pigment dots (PDs) in acquired melanocytic naevi. In a consecutive series of 189 patients (median age 28 years; range 10-73 years) with one or more naevi as diagnosed on D-ELM, we evaluated 35 solitary lesions and one naevus randomly selected from each of the 154 patients with multiple lesions. D-ELM images were classified for the presence or absence of PN, BGs and PDs on two blind readings. Data analysis was based on multiple logistic regression. Patient age was positively associated with PN and inversely associated with BGs. The probability of PN increased with more than 110 days since last exposure to the sun, whereas a rapid decrease for BGs and PDs was observed after approximately 1 month. PDs were significantly more likely among lesions with 6-10 h/day of recent exposure. Sex, total lifetime hours of exposure, sunbed use, skin type and colour of hair exerted no effect. In conclusion, major D-ELM features appeared to differ in their relationship with sun exposure indicators.
Association between germ cell tumours, large numbers of naevi, atypical naevi and melanoma.
Avril MF, Chompret A, Verne-Fourment L … +6 more , Terrier-Lacombe MJ, Spatz A, Fizazi K, Bressac-de Paillerets B, Demenais F, Théodore C
Melanoma Res · 2001 Apr · PMID 11333120 · Publisher ↗
Identifying groups of subjects at high risk for the development of melanoma is crucial for the early diagnosis of curable tumours. In the present study, we performed a skin examination in a group of 63 patients followed...
Identifying groups of subjects at high risk for the development of melanoma is crucial for the early diagnosis of curable tumours. In the present study, we performed a skin examination in a group of 63 patients followed up after treatment of germ cell tumours (GCTs) who were referred to the dermatologist for multiple pigmented cutaneous spots. Forty-nine patients bearing a great number of naevi or atypical naevi were included in the study. Two thin cutaneous melanomas were discovered in two patients. In addition, a third patient had had a conjunctival melanoma since treatment of the GCT. Our study confirms the presence of atypical naevi in a subgroup of GCT patients, who are shown to be at high risk of developing melanoma. Patients harbouring multiple pigmented spots should be referred for a skin examination aimed at early detection of curable melanomas, and should be advised to protect themselves from sun exposure.
Differentiation between pigmented Spitz naevus and melanoma by digital dermoscopy and stepwise logistic discriminant analysis.
Rubegni P, Ferrari A, Cevenini G … +9 more , Piccolo D, Burroni M, Perotti R, Peris K, Taddeucci P, Biagioli M, Dell'Eva G, Chimenti S, Andreassi L
Melanoma Res · 2001 Feb · PMID 11254114 · Publisher ↗
Epiluminescence light microscopy (ELM) has proven useful in the diagnosis of pigmented skin lesions (PSLs). However, in some cases this technique does not sufficiently increase the diagnostic accuracy in distinguishing p...
Epiluminescence light microscopy (ELM) has proven useful in the diagnosis of pigmented skin lesions (PSLs). However, in some cases this technique does not sufficiently increase the diagnostic accuracy in distinguishing pigmented Spitz naevi (PSNs) from melanoma. With the aim of obviating these problems of qualitative interpretation, methods based on the mathematical analysis of PSLs, such as digital dermoscopy analysis (DDA), have recently been developed. In the present study we used a digital dermoscope (DBDermo-MIPS, Dell'Eva-Burroni) to analyse PSNs and melanomas with similar clinical and dermoscopic features for any correlation between variables and to determine its discriminating power with respect to histological diagnosis. The 100 lesions underwent histological examination by three experienced dermatopathologists and were identified as PSNs (43) or melanomas (57). Thirty-six parameters were identified as possible discriminating variables and were grouped in four categories: geometry, colour, texture, and islands of colour. Statistical analysis was used to identify the variables with the highest discriminating power. Stepwise discriminant analysis selected only four variables: entropy, minimum diameter, red lesion value and peripheral dark (the means of these variables were higher in melanomas than in PSNs). Thus the combined use of digital dermoscopy and stepwise logistic discriminant analysis made it possible to single out the best objective variables for distinguishing PSN and melanoma.
Establishment of IPC 227 cells as human xenografts in rabbits: a model of uveal melanoma.
Bonicel P, Michelot J, Bacin F … +5 more , Papon J, Kemeny JL, Moins N, Morvan D, Madelmont JC
Melanoma Res · 2000 Oct · PMID 11095405 · Publisher ↗
This study was designed in order to evaluate the feasibility of establishing an animal model of human uveal melanoma. IPC227, a cell line established from the biopsy of a patient with a spindle cell ciliary body melanoma...
This study was designed in order to evaluate the feasibility of establishing an animal model of human uveal melanoma. IPC227, a cell line established from the biopsy of a patient with a spindle cell ciliary body melanoma, was transplanted into the anterior chamber of the eye in immunosuppressed New Zealand rabbits. In a second step, a tumour fragment from the anterior chamber was implanted transclerally into the posterior choroid. Complete ophthalmological examinations were then performed on the animals. Characteristic growth patterns were noted depending on the location of implantation. In the anterior chamber, diffuse, flat, heavily pigmented tumours appeared 8 days after the injection of the cell suspension that covered the iris and the angle by day 25, with a success rate of 100%. Nodular, lightly pigmented tumours were obtained 6-7 weeks after subchoroidal implantation, with a 25% success rate. Clinical examination, including fundus photography, ultrasound and magnetic resonance imaging, demonstrated the same characteristics as those of human uveal melanoma, confirming the value of this model for the evaluation of new therapeutic and diagnostic methods in the management of uveal melanoma.
Immunodetection of gastrin-releasing peptide in malignant melanoma cells.
Charitopoulos KN, Lazaris AC, Aroni K … +3 more , Kavantzas N, Nikolakopoulou E, Davaris P
Melanoma Res · 2000 Aug · PMID 10985675 · Publisher ↗
Gastrin-releasing peptide (GRP), the mammalian counterpart of bombesin, was first identified in the nervous system of the gastrointestinal tract. Little is known about its distribution in the human skin or about its func...
Gastrin-releasing peptide (GRP), the mammalian counterpart of bombesin, was first identified in the nervous system of the gastrointestinal tract. Little is known about its distribution in the human skin or about its function in certain diseases such as malignant melanoma. Recently functional GRP receptors have been found on human melanoma cell lines. We therefore investigated, using immunohistochemistry, whether human melanoma cells express GRP and whether there is a significant change in its distribution among the different clinical types of melanoma and a connection to histopathological features such as growth phase, type of malignant cells, Breslow thickness and Clark level of invasion. We demonstrated the existence of GRP in all clinicopathological types of melanoma; a predilection for quantitatively increased GRP immunostaining was noticed in nodular melanomas (P = 0.007). As well as this, we observed a restriction of GRP expression at a specific level of invasion, i.e. within the reticular dermis (Clark IV) (P = 0.032). GRP immunoreactivity was found to be associated with an increased amount of melanin pigment in malignant cells (P = 0.054). The presence of GRP in malignant melanocytes, along with its association with the various histopathological features, suggests that GRP may play a role in the pathophysiology of this type of cutaneous tumour.
Minimal deviation and/or naevoid melanoma: is recognition worthwhile? A clinicopathological study of nine cases.
Stas M, van den Oord JJ, Garmyn M … +3 more , Degreef H, De Wever I, De Wolf-Peeters C
Melanoma Res · 2000 Aug · PMID 10985672 · Publisher ↗
One to two per cent of primary cutaneous melanomas share clinical features with benign melanocytic and non-melanocytic skin lesions, and even at histology recognition of their malignant nature is problematic, mainly due...
One to two per cent of primary cutaneous melanomas share clinical features with benign melanocytic and non-melanocytic skin lesions, and even at histology recognition of their malignant nature is problematic, mainly due to the lack of an intraepithelial component, their nodular aspect and the monotonous cell population throughout the lesion. These tumours were termed minimal deviation melanomas (MDMs) by Reed et al. and later naevoid melanomas by Schmoeckel et al. The name MDM suggests the concept of a more favourable outcome for these melanomas that do not (yet) show the typical features of fully evolved lesions able to metastasize, although naevoid melanomas seem to behave like 'common' melanomas. In a retrospective analysis of nine cases of MDM collected from our database and followed for a median duration of 112 months, we faced similar clinical and histological pitfalls and observed local recurrence following marginal resection. Wide excision, even of local recurrence, and therapeutic node dissection could nevertheless provide survival comparable at least to that predicted by mathematical models for patients who initially had optimal treatment.
Lessons from melanocyte development for understanding the biological events in naevus and melanoma formation.
Herlyn M, Berking C, Li G … +1 more , Satyamoorthy K
Melanoma Res · 2000 Aug · PMID 10985664 · Publisher ↗
Recent advances in mouse genetics have identified molecular changes that are critical for melanocyte maturation and differentiation. This review briefly summarizes the current knowledge of distinct steps in melanocyte de...
Recent advances in mouse genetics have identified molecular changes that are critical for melanocyte maturation and differentiation. This review briefly summarizes the current knowledge of distinct steps in melanocyte development, and identifies for each step the most important molecules such as the growth factors stem cell factor and endothelin-3, with their respective receptors. Classical cadherins, i.e. E-cadherin, N-cadherin and P-cadherin, determine melanocyte positioning in the skin. During naevus and melanoma development, the two growth factor signalling pathways are downregulated, whereas cadherin expression shifts concomitantly with re-positioning of the naevus and melanoma cells in the skin. Loss of E-cadherin and gain of N-cadherin by melanoma cells has profound consequences for the regulatory cross-talk between various types of cells in the skin. Naevus and melanoma cells that do not express E-cadherin are resistant to control by keratinocytes and establish close communications with fibroblasts and endothelial cells. However, forced expression of E-cadherin in melanoma cells can reverse the malignant phenotype by re-establishing the control of keratinocytes over the melanoma cells. Even highly aggressive metastatic melanoma cells can be signalled to turn off the expression of genes associated with tumour invasion and metastasis, suggesting that this strategy could be utilized in the therapy of melanoma.
Epiluminescence microscopy features of cutaneous malignant melanoma metastases.
Schulz H
Melanoma Res · 2000 Jun · PMID 10890382
Especially small and/or initial cutaneous malignant melanoma metastases (CMMMs) are tumours with inconspicuous clinical and sometimes histological features which may be difficult to differentiate from benign melanocytic...
Especially small and/or initial cutaneous malignant melanoma metastases (CMMMs) are tumours with inconspicuous clinical and sometimes histological features which may be difficult to differentiate from benign melanocytic lesions or angiomas. Thus it would be very valuable to have additional criteria for the differential diagnosis of such lesions. Thirty histologically verified CMMMs were examined using epiluminescence microscopy (ELM) in order to visualize a large number of morphological features permitting the recognition of malignancy. One hundred primary cutaneous malignant melanomas (PCMMs), 50 dysplastic naevi, 50 common naevi, 30 blue naevi and 20 haemangiomas served as the control group; these were randomly selected from a large data base and were all reviewed for histological diagnosis. Four of the 24 features studied were shown to differ significantly between CMMMs and the control group. Two features of the malignant tumour group (CMMM and PCMM) differed significantly from the benign tumour group. A polymorphic angiectatic base pattern and/or vascular aneurysms, peripheral erythema, brown-grey coloration as a negative criterion (i.e. its absence is indicative of CMMM) and a light brown halo had a specificity of 86.7-96.0% for CMMM. Areas of polymorphic and/or horizontally dilated capillaries and a saccular pattern had a specificity of 97.3-99.2% for the malignant group (CMMM and PCMM). Three features - peripheral greyish patches, lesions surrounded by grey streaks (melanoma cell infarcts of the vessels) and microscopic ovoid blood lakes (spontaneous microhaemorrhages)--were absent in the benign group. The prevalence of distinct ELM criteria in CMMM represents a useful enhancement for the diagnosis of malignancy in melanocytic skin lesions.
Animal models of uveal melanoma.
Dithmar S, Albert DM, Grossniklaus HE
Melanoma Res · 2000 Jun · PMID 10890373
Many attempts have been made to develop a suitable animal model to study more effectively the aetiology, pathogenesis, diagnosis and therapy of intraocular (uveal) melanoma. Uveal melanoma may spontaneously occur in some...
Many attempts have been made to develop a suitable animal model to study more effectively the aetiology, pathogenesis, diagnosis and therapy of intraocular (uveal) melanoma. Uveal melanoma may spontaneously occur in some animals, including dogs, cats, horses, rats, mice, birds and fish. The histological features, metastatic behaviour and unpredictable nature of occurrence of these uncommon spontaneous tumours detract from their suitability as a model. Several methods have been developed to induce intraocular melanoma chemically or by radiation in laboratory animals. Some of these induced tumours resemble human uveal melanoma, although the majority originate from the retinal pigment epithelium. Uveal proliferations have been biologically induced by feline leukaemia/sarcoma virus and simian virus 40, although the presence of virus in tumour cells and extraocular tumours resulting from shed virus detract from the utility of this model. Inoculation of tissue culture hamster, murine or human melanoma cells into animal eyes has the advantage that the inoculation site and size of inoculum can be controlled. Disadvantages include the immune suppression necessary for tumour growth in some models as well as the fact that many of the melanoma cell lines are of cutaneous origin. Transgenic murine models have been developed using the promoter region of the tyrosinase gene to target expression of oncogenes in melanin-producing cells. Spontaneous intraocular pigmented tumours and distant metastases may occur, although many, if not all, of the intraocular tumours arise in the retinal pigment epithelium.
Contrast-enhanced high resolution magnetic resonance imaging of pigmented malignant melanoma using Mn-TPPS4 and Gd-DTPA: experimental results.
Mäurer J, Strauss A, Ebert W … +2 more , Bauer H, Felix R
Melanoma Res · 2000 Feb · PMID 10711639
The aim of this study was to evaluate the potential of the paramagnetic metalloporphyrin Mn-TPPS4 (using Gd-DTPA as the reference) for magnetic resonance imaging (MRI) of pigmented malignant melanoma in an animal model....
The aim of this study was to evaluate the potential of the paramagnetic metalloporphyrin Mn-TPPS4 (using Gd-DTPA as the reference) for magnetic resonance imaging (MRI) of pigmented malignant melanoma in an animal model. High resolution MRI (2.0 T, 2.0 cm surface coil, T1-weighted FLASH two-dimensional sequence) was performed on 15 mice (C57bl6) with intracutaneous implanted melanoma (B16F1) before and after intravenous administration of Gd-DTPA (Magnevist, Schering AG, Berlin, Germany) and Mn-TPPS4 (Porphyrin Products, Logan, Utah, USA). The images were evaluated quantitatively by calculating the percentage enhancement, the slope of the signal intensity-to-time curves, the percentage increase in the signal intensity, and the signal-to-noise and contrast-to-noise ratios. The qualitative evaluation was accomplished by visual assessment of the enhancement, the demarcation of the tumours from the surrounding tissue, and the homogeneity of the tumours. Contrast medium-enhanced images showed an increase in signal intensity for all the tumours, with no significant difference between the contrast media. Specific accumulation of the contrast media in the melanoma could not be proved. Demarcation of tumours from the surrounding tissue is better after administration of contrast media; regressive changed areas were better depicted.
Experimental ruthenium plaque therapy of amelanotic and melanotic melanomas in the hamster eye.
Urbanska K, Romanowska-Dixon B, Elas M … +7 more , Pajak S, Paziewski E, Bryk J, Kukielczak B, Slominski A, Zygulska-Mach H, Lukiewicz S
Melanoma Res · 2000 Feb · PMID 10711637
The effects of beta-radiation on melanoma implanted into the hamster's eye were investigated. Two Bomirski hamster melanomas (BHMs), differing in their melanin content, were compared with regard to their radiosensitivity...
The effects of beta-radiation on melanoma implanted into the hamster's eye were investigated. Two Bomirski hamster melanomas (BHMs), differing in their melanin content, were compared with regard to their radiosensitivity to ruthenium-106 (106Ru) radiation. Tumours growing in the iris were irradiated with 3, 6 or 10 Gy of 106Ru given as a single dose or in four fractions at 24 h Intervals. Tumour growth kinetics and distant metastases were studied, and the eyeballs were examined histologically. Dose-dependent delay of tumour growth was observed in both melanomas. After treatment with a dose of 6 Gy, the Ab amelanotic tumours grew 2.6 times slower, and the Ma melanotic tumours 1.4 times slower than untreated ones. The location of metastases differed in the two tested lines--pigmented metastases were found mainly in the lungs, while unpigmented metastases were found mainly in the kidneys. Histopathological analysis showed signs of blood vessel damage such as endothelial cells swelling, erythrocyte extravasation and tumour necrosis. This last finding increased with the rising dose of beta-radiation. Pigmented tumours were found to be two times more resistant to beta-radiation than amelanotic ones. The pattern of metastases of BHMs is determined by the type of melanoma (Ab or Ma). Exposure to beta-radiation from 106Ru did not significantly affect either the number or size of metastases except at a dose of 10 Gy. This dose caused a statistically significant decrease in the number of metastases in the Ma melanotic subline.
Comparison of in vitro cytotoxicity of N-acetyl and N-propionyl derivatives of phenolic thioether amines in melanoma and neuroblastoma cells and the relationship to tyrosinase and tyrosine hydroxylase enzyme activity.
Gili A, Thomas PD, Ota M … +1 more , Jimbow K
Melanoma Res · 2000 Feb · PMID 10711635
Our laboratory has synthesized two new phenolic thioether amines, N-propionyl-4-S-cysteaminylphenol (N-Pr-4-S-CAP) and N[2-[(4-propionyloxyphenyl)thio]ethyl] propionamide (N,O-diPr-4-S-CAP). These compounds, along with t...
Our laboratory has synthesized two new phenolic thioether amines, N-propionyl-4-S-cysteaminylphenol (N-Pr-4-S-CAP) and N[2-[(4-propionyloxyphenyl)thio]ethyl] propionamide (N,O-diPr-4-S-CAP). These compounds, along with the previously described phenolic thioether amine N-acetyl-4-S-cysteaminylphenol (N-Ac-4-S-CAP) and its acetyl form (N,O-diAc-4-S-CAP), are tyrosine-amine derivative analogues. The cytotoxicity of these compounds is thought to be tyrosinase dependent, which may make them suitable for targeted anti-melanoma therapy since only melanocytes and their malignant counterparts contain this active enzyme. To further investigate this hypothesis, we performed MTT [3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide] assays to determine the cytotoxicity of these compounds in 10 different cell lines. Specifically, we examined to what extent cytotoxicity is related to tyrosinase and tyrosine hydroxylase activity using melanoma and neuroblastoma cells, which have a common metabolic pathway using tyrosinase and tyrosine hydroxylase, respectively. The most sensitive cell line was the highly pigmented SK-MEL-23 melanoma cell line, which shows a very high tyrosinase activity with the highest melanin pigmentation. KAN and SK-NSH (two neuroblastoma cell lines), which have no tyrosinase activity but high tyrosine hydroxylase, were also sensitive. However, C32 (a non-pigmented melanoma with a lower tyrosinase activity) was also sensitive, and MeWo (a moderately pigmented melanoma with a high tyrosinase activity) was less sensitive. This in vitro study may indicate that there is a non-tyrosinase-mediated mechanism of cytotoxicity for phenolic thioether amines in addition to the tyrosinase-mediated one described previously.
Decreased density of epidermal dendritic cells in melanocytic naevi: the possible role of in vivo sun exposure.
Azizi E, Schwaaf A, Lazarov A … +8 more , Shifer O, Lublin A, Pavlotsky F, Trau H, Lusky A, Topaz M, Engelberg S, Broecker EB
Melanoma Res · 1999 Oct · PMID 10596919 · Publisher ↗
Melanocytic naevi are benign skin tumours that originate in the epidermis. The pathogenesis of naevi and cutaneous malignant melanoma has been linked to sun exposure. This study evaluates alterations in the density of im...
Melanocytic naevi are benign skin tumours that originate in the epidermis. The pathogenesis of naevi and cutaneous malignant melanoma has been linked to sun exposure. This study evaluates alterations in the density of immunologically active epidermal dendritic cells (EDCs) in naevi in response to sun exposure. Immunohistologically stained sections of 266 naevi from patients from Israel (n=135) and Germany (n=131) were evaluated. The proportion of naevi with decreased density of HLA-DR+ (dDR+) and CD1a+ (dCD1a+) EDCs was analysed according to country, last exposure to sunlight, anatomical location and histological subtype. The risk of dDR+ was found to be linked to residence in Israel compared with Germany (odds ratio [OR] = 4.2; 95% confidence interval [CI] = 2.0-8.9), suggesting a latitude-dependent effect. Naevi removed in summer had a higher risk of dCD1a+ (OR = 4.7; 95% CI = 2.3-9.8) compared with those removed in winter. The most conspicuous dDR+ among the German cases, and dCD1a+ among the Israelis, occurred in naevi located on commonly exposed skin. The similar densities of EDCs in the lesional and perilesional skin of the majority of the naevi indicates that the underlying naevus cells have no effect on EDC density. It is not unlikely that an altered immune response due to dDR+ and dCD1a+ in sun-exposed skin in the vicinity of naevi contributes to the subsequent melanoma risk in highly susceptible individuals.
Expression of tyrosinase, TRP-1 and TRP-2 in ultraviolet-irradiated human melanomas and melanocytes: TRP-2 protects melanoma cells from ultraviolet B induced apoptosis.
Nishioka E, Funasaka Y, Kondoh H … +3 more , Chakraborty AK, Mishima Y, Ichihashi M
Melanoma Res · 1999 Oct · PMID 10596909 · Publisher ↗
Tyrosinase related protein (TRP)-1 and TRP-2 are known to regulate the quality of melanin, and recently their potential role in inhibiting apoptosis have also been reported. To study the role of tyrosinase, TRP-1 and TRP...
Tyrosinase related protein (TRP)-1 and TRP-2 are known to regulate the quality of melanin, and recently their potential role in inhibiting apoptosis have also been reported. To study the role of tyrosinase, TRP-1 and TRP-2 in the growth, differentiation and cell death of ultraviolet B (UVB) irradiated melanocytes, the expression of these proteins in amelanotic and melanotic cells was examined. Expression of tyrosinase and TRP-1 correlated with melanin content, which was upregulated after repeated irradiation of melanotic cells by low doses of UVB. In contrast, the expression and activity of TRP-2 correlated with cell proliferation, but not with pigmentation. In one melanotic melanoma cell line, significant suppression of cell proliferation was observed after low or high doses of UVB irradiation, possibly due to apoptotic changes. TRP-2 expression was remarkably reduced in UVB-irradiated cells, and transfection with TRP-2 expression vector rescued these cells from UVB-induced apoptosis. These results indicate that TRP-2 expression is closely associated with the regulation of cell growth/survival of melanocytes exposed to UVB and that TRP-2 plays a role in protecting melanoma cells from UVB-induced apoptosis.
Mapping of occult melanoma micrometastases in the inguinal lymph node basin by immunohistochemistry and RT-PCR.
Hatta N, Fujimoto A, Takehara K … +1 more , Takata M
Melanoma Res · 1999 Aug · PMID 10504060 · Publisher ↗
To examine the distribution of occult micrometastases that could be potential sources of recurrence, complete maps of microscopic and submicroscopic metastases in entire inguinal lymph node basins were generated in 13 me...
To examine the distribution of occult micrometastases that could be potential sources of recurrence, complete maps of microscopic and submicroscopic metastases in entire inguinal lymph node basins were generated in 13 melanoma patients who had undergone elective or therapeutic lymphadenectomy. Occult micrometastases were analysed immunohistochemically for the pigment cell-specific antigen HMB-45 in all 155 nodes and using a reverse transcriptase-polymerase chain reaction (RT-PCR) assay to detect tyrosinase mRNA in 35 nodes. Five patients were determined to be node-negative by routine histopathology; three of these subjects were also negative by RT-PCR and/or immunohistochemistry. However, the remaining two patients had occult metastases, which were confined to a possibly sentinel node in one and were detected in multiple nodes in the other. Eight patients had histological evidence of lymph node metastasis. Three of these patients had no additional detectable submicroscopic disease, and one had occult metastasis in one node adjacent to the histologically positive node. In contrast, the other four patients had occult micrometastases in multiple non-sentinel, higher level nodes. The two patients who relapsed belonged to this group. The results show considerable variation in the distribution pattern of occult metastases in the regional lymph nodes, and have significant implications for the role of regional lymph node dissection, including sentinel node mapping with selective lymphadenectomy, in the management of melanoma patients.
Gamma radiation and MC540 photosensitization of melanoma in the hamster's eye.
Kukielczak B, Romanowska B, Bryk J
Melanoma Res · 1999 Apr · PMID 10380933 · Publisher ↗
The purpose of this study was to evaluate the effects of cobalt-60 gamma-radiation and argon laser irradiation using injected merocyanine (MC540) as a photosensitizer on pigmented and non-pigmented Bomirski hamster melan...
The purpose of this study was to evaluate the effects of cobalt-60 gamma-radiation and argon laser irradiation using injected merocyanine (MC540) as a photosensitizer on pigmented and non-pigmented Bomirski hamster melanomas growing in the eye. The animals were treated with one of four regimens, receiving gamma-irradiation only, photosensitization only, a combination of gamma-irradiation and photosensitization, or a combined time-fractionated treatment. Tumours were exposed to laser light 24 h after injection, when the photosensitizing dye concentration was highest. The degree of tissue damage was evaluated by observation of the area for necrosis, interruption of blood circulation, and the shape and dissemination of the tumour cells. Additionally, tumour growth was monitored through the measurement of tumour volume and also calculated from histological cross sections on the assumption that the tumour morphology is hemi-ellipsoidal. A single treatment of tumours by a combination of photodynamic therapy and ionizing radiation resulted in an additive effect, inhibiting tumour growth for 2-4 days. A time-fractionated treatment, given four times every 24 h, markedly delayed tumour growth for up to 6 weeks. The results indicate that MC540-mediated photodynamic treatment in combination with gamma-radiation exerts a significant therapeutic effect on a rapidly growing melanoma.
The presence of melanin in genomic DNA isolated from pigmented cell lines interferes with successful polymerase chain reaction: a solution.
Price K, Linge C
Melanoma Res · 1999 Feb · PMID 10338329 · Publisher ↗
We have found that polymerase chain reaction (PCR) amplification of genetic material is unsuccessful when using template genomic DNA derived from certain normal melanocyte and melanoma cell lines. We demonstrated that th...
We have found that polymerase chain reaction (PCR) amplification of genetic material is unsuccessful when using template genomic DNA derived from certain normal melanocyte and melanoma cell lines. We demonstrated that this phenomenon only occurs with pigmented cell lines and appears to be due to the association of genomic DNA with remnants of the pigment melanin. We therefore describe a simple and rapid technique that rids genomic DNA samples of melanin, resulting in a genomic DNA template that allows successful PCR.
Parallel risk assessment of melanoma and basal cell carcinoma: skin characteristics and sun exposure.
Rosso S, Zanetti R, Pippione M … +1 more , Sancho-Garnier H
Melanoma Res · 1998 Dec · PMID 9918420 · Publisher ↗
In this study we compared the strength of the association of constitutional factors and sun exposure with cutaneous malignant melanoma (CMM) and basal cell carcinoma (BCC). We analysed 260 incident cases of CMM, 425 inci...
In this study we compared the strength of the association of constitutional factors and sun exposure with cutaneous malignant melanoma (CMM) and basal cell carcinoma (BCC). We analysed 260 incident cases of CMM, 425 incident cases of BCC and two sets of population controls from previous case-control studies conducted in Turin, Italy. Simultaneous comparison was accomplished by comparing separate simple logistic and polytomous logistic regressions. Tendency to sunburn was shown to be the most important risk indicator for both types of tumours, being associated with a two- to three-fold increase in risk for CMM and a two-fold increase in risk for BCC. Intermittent and intense sun exposure, as during beach holidays, increased the risk of both CMM and BCC, while prolonged exposure to sun, as during outdoor occupations, was not associated with CMM or BCC. The increase in risk during beach holidays occurred mainly during childhood for CMM cases, while for BCC cases it also continued during adulthood. Analysis of the independent effect of risk factors confirmed the role of skin phenotype (eye colour odds ratio [OR] = 1.6, tendency to sunburn OR = 2.1) and intermittent sun exposure (sunburns in childhood OR = 3.8, sun exposure during beach holidays OR = 1.2) in CMM. Risk of CMM showed a significant increase when sun exposure exceeded the threshold of about 3500 h during beach holidays cumulated in a lifetime. In contrast, the role of skin phenotype in BCC is less strong, but cumulated hours of sun exposure during beach holidays in a lifetime showed a constant risk rise with an early plateau at a low exposure level.
Loss of expression or mutations in the p73 tumour suppressor gene are not involved in the pathogenesis of malignant melanomas.
Kroiss MM, Bosserhoff AK, Vogt T … +4 more , Buettner R, Bogenrieder T, Landthaler M, Stolz W
Melanoma Res · 1998 Dec · PMID 9918412 · Publisher ↗
Recently p73, a novel p53 homologous tumour suppressor gene, has been cloned and mapped to chromosome 1p36. Like p53, important functions of p73 in controlling the cell cycle and programmed cell death have been described...
Recently p73, a novel p53 homologous tumour suppressor gene, has been cloned and mapped to chromosome 1p36. Like p53, important functions of p73 in controlling the cell cycle and programmed cell death have been described. Loss of p73 has been demonstrated in neuroblastomas and its involvement in tumorigenesis has been suggested to occur in other neuroectodermal cancers. Since genetic alterations at the tumour suppressor locus 1p36 have been also identified in malignant melanomas, we investigated the expression of p73 in a panel of nine different human melanoma cell lines, 17 melanocytic naevi, 17 primary malignant melanomas and 20 metastases by reverse transcriptase polymerase chain reaction (PCR) and Southern blotting. We observed significant p73 mRNA expression in all the cell lines and tissue specimens except one benign melanocytic naevus and one melanoma metastasis. Sequencing the PCR fragments of nine melanoma cell lines derived from primary tumours and five metastases over the entire p73 DNA binding domain revealed wild-type sequences in all cases. In summary, we conclude that loss of p73 mRNA expression or mutations in the p73 DNA binding domain do not represent common genetic events involved in the pathogenesis of malignant melanomas.
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