Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1522102 (Melanoma)
 7,698 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The events occurring during the penetration of melanoma cells through the dermal-epidermal junction, which is the first crucial step in the process of metastasis, are poorly understood, partly because no suitable tissue models exist. In the in vitro model reported here, two melanoma clones (T1C3, which generates lung metastases in experimental animals, and IC8, which does not) derived from a single parental cell line were co-seeded with normal allogenic keratinocytes onto acellular human de-epidermized dermis with preserved intact basement membrane and cultured for up to 1 month at an air-liquid interface. Histological, immunohistochemical and ultrastructural studies showed that melanoma cells from the metastatic clone (T1C3), but not from the non-metastatic clone (IC8), penetrated the dermal-epidermal junction to invade the dermis after 3 weeks of culture. Local invasion was associated with the dissolution of the native epidermal basement membrane collagens type IV and VII. Confocal laser scanning microscopy analysis demonstrated that numerous T1C3 cells were able to colonize the interstitial dermis and to rapidly penetrate empty dermal cavities. Our model represents a significant technical advance over others currently available since: (i) the organized three-dimensional architecture of the native dermal-epidermal junction is preserved; (ii) the active invasion process coincides with the dissolution of native components of the epidermal basement membrane, i.e. collagen types IV and VII; and (iii) the ability of melanoma cells to cross the dermal-epidermal junction correlates with their metastatic potential. This model provides a valuable tool for the study of the time-course of the cellular and molecular events that occur during the earliest steps of invasion in cutaneous melanoma. It also offers new opportunities to study the possible role of the keratinocyte environment in melanoma invasion.
Melanoma Res 2000 Oct
PMID:Penetration of human metastatic melanoma cells through an authentic dermal-epidermal junction is associated with dissolution of native collagen types IV and VII. 1109 3

Sentinel lymph node biopsy was attempted in 336 patients with clinically node-negative cutaneous melanoma. All patients were injected with technetium-99m labelled radiocolloid, with 108 patients simultaneously receiving vital blue dye for sentinel node identification. Sentinel lymph nodes were identified in 329 patients, giving a technical success rate of 97.9%. Metastatic disease was identified in 39 (11.9%) of the patients in whom sentinel nodes were found. Patients with negative sentinel nodes were observed and patients with positive sentinel nodes underwent comprehensive lymph node dissection. The presence of metastatic disease in the sentinel nodes and primary tumour depth by Breslow or Clark levels were joint predictors of survival based on Cox proportional hazards modelling. Disease recurrences occurred in 26 (8.8%) patients with negative sentinel lymph nodes, with isolated regional recurrences as the first site in 10 (3.4%). No patients with Clark level II primary tumours were found to have positive sentinel nodes or disease recurrences. One patient with a thin (<0.75 mm) Clark level III primary had metastatic disease in a sentinel node. Patients with metastases confined to the sentinel nodes had similar survival rates regardless of the number of nodes involved.
Melanoma Res 2001 Feb
PMID:Gamma probe guided biopsy of the sentinel node in malignant melanoma: a multicentre study. 1125 15

Various histopathological techniques have been developed in order to improve the detection of micrometastasis in the regional lymph nodes of patients with malignant melanoma. Our standard histopathological examination of lymph nodes included haematoxylin and eosin (H & E) staining and immunohistochemistry (IH) using antibodies to HMB-45 and S-100 proteins of three paraffin sections at one level. In addition, lymph nodes were examined by molecular biological methods using tyrosinase reverse transcription-polymerase chain reaction (RT-PCR). In this study, we investigated the use of step sections and IH in lymph nodes regarded as negative by standard histopathology but positive by tyrosinase RT-PCR, suggesting the presence of tumour cells. In a series of 76 consecutive patients with stage I and II cutaneous melanoma, a total of 156 regional lymph nodes were examined by H & E staining, IH and tyrosinase RT-PCR. All lymph nodes were bisected along their long axis for separate evaluation. In 21 patients, at least one lymph node in the regional nodal basin reported as tumour-negative by standard histopathology was demonstrated to express tyrosinase (total number of nodes = 33). These 33 lymph nodes were re-examined by H & E and IH at 10 additional levels of the paraffin block. Only one lymph node from one patient had occult melanoma cells in deeper levels detected exclusively by IH. Six out of 20 patients with positive findings exclusively on tyrosinase RT-PCR developed tumour recurrences during a median follow-up of 34 months. We therefore conclude that additional step sectioning with IH does not significantly increase the detection of tumour-positive lymph nodes. Patients with melanoma cells detected exclusively by RT-PCR, however, were shown to be at increased risk for tumour recurrence.
Melanoma Res 2001 Feb
PMID:Does intensive histopathological workup by serial sectioning increase the detection of lymph node micrometastasis in patients with primary cutaneous melanoma? 1125 16

The number and size of melanocytic naevi are the main predictors of cutaneous melanoma. Naevus development per unit of skin surface is greatest during childhood. We assessed the body distribution of naevi 2-4.9 mm and > or = 5 mm in 649 European children aged 6-7 years old from Brussels (Belgium), Bochum (Germany), Lyon (France) and Rome (Italy). The numbers of naevi 2-4.9 mm and naevi > or = 5 mm were strongly correlated, especially on the trunk. For naevi 2-4.9 mm, the highest relative densities were found on the face, back, shoulders and the external surface of the arms. The lowest relative densities were found on the hands, legs, feet and abdomen. The relative density of naevi > or = 5 mm was higher on the trunk than on any other body site. Similar body distributions were observed in both sexes and at each centre. The body site distribution of naevi 2-4.9 mm seemed to parallel the usual sun exposure patterns of young European children. It is suggested that the development of naevi > or = 5 mm might be a marker of the vulnerability of melanocytes to the harmful effects of solar radiation. Vulnerability would be maximal on the back, and would decrease from proximal to distal skin areas, with melanocytes of the hands and feet having the lowest vulnerability. The number of naevi acquired on a specific area of skin would result from the combined effects of local vulnerability to solar radiation and local sun exposure history. The origin of acquired body site differences in the susceptibility of melanocytes to ultraviolet radiation is unknown, although it seems to parallel the body site density of sensory innervation.
Melanoma Res 2001 Apr
PMID:The body site distribution of melanocytic naevi in 6-7 year old European children. 1133 21

We studied familial risks in cutaneous melanoma by comparing the occurrence of melanoma, or discordant cancer, in two generations, based on the Swedish Family-Cancer Database of 9.6 million individuals. Offspring were from 0 to 61 years of age. Cancers were obtained from the Swedish Cancer Registry for the years 1958 to 1996. The study was based on 30,170 cases of melanoma. Among these, 196 offspring came from families where a parent also presented with melanoma. The overall familial hazard ratio (FHR) was 2.47 when a parent had melanoma; an early age of onset increased the risk. Multiple primary melanomas in parents increased the FHR in offspring, being 2.23 for one, 9.10 for two and up to 83 for more than two melanomas in the parent. The number of affected offspring increased the risk of melanoma in the parents, from 3.05 when one was affected to 5.12 and 151 when two or three offspring were affected, respectively. Melanoma risk to a sibling with an affected proband was 3.56. Melanoma in one generation was associated with an increased occurrence of squamous cell carcinoma of the skin in the other generation. Other weaker associations were found to pancreatic, breast, testicular and nervous system cancers and non-Hodgkin lymphomas.
Melanoma Res 2001 Apr
PMID:A population-based study of familial cutaneous melanoma. 1133 22

Epiluminescence microscopy (ELM), or dermatoscopy, is a non-invasive technique for the diagnosis of cutaneous melanoma that may play a role in the non-invasive, preoperative assessment of melanoma thickness. This study investigated the correlation between the frequency of appearance of some standard ELM criteria and the histological thickness of melanomas. In addition, the possible role of the total dermoscopic score (TDS) according to ABCD rule of dermoscopy as a predictor of melanoma thickness was analysed. The dermoscopic images of 84 cutaneous melanomas were retrospectively investigated to evaluate the presence of 10 standard ELM criteria, and for each lesion the TDS was established (with observers blinded as to the tumour thickness). A statistically significant association was found between the presence of an irregular pigment network and melanomas with a Breslow index equal to or lower than 0.75 mm (positive predictive value of 68%); in contrast, radial streaming, atypical vascular pattern and grey-blue areas were associated with melanomas > 0.75 mm (positive predictive values of 77%, 65% and 70%, respectively). Of the melanomas thinner than 0.76 mm, 82% showed a TDS lower than 6.80 (optimized cut-off point), while 79% of melanomas thicker than 0.75 mm had a TDS higher than 6.80 (chi2 = 30.815, P < 0.001); the positive predictive value of a TDS > 6.80 in the detection of lesions thicker than 0.75 mm was 79%. In conclusion, a statistically significant correlation does exist between some dermoscopic features and melanoma thickness. Both the mostly used dermoscopic methods (standard ELM pattern analysis and the ABCD rule of dermatoscopy) may provide useful information in the non-invasive assessment of melanoma thickness. However, their diagnostic performance is far from 100%; further studies are needed to investigate whether the combination of dermoscopy with other non-invasive approaches (e.g. sonometry) may result in an overall improvement in the diagnostic performance.
Melanoma Res 2001 Apr
PMID:Non-invasive analysis of melanoma thickness by means of dermoscopy: a retrospective study. 1133 24

Although many statistical models have been developed to predict survival in cutaneous melanoma, few predict the end point of regional lymph node metastasis shortly after the diagnosis of melanoma. We used routine clinical and histologic data from 573 patients referred to the Duke University Melanoma Clinic, Durham, NC, during the 1980s and 1990s who underwent lymph node resections during the first year after the diagnosis of primary cutaneous melanoma. The outcome we modeled (using the logistic regression model) was the probability of lymph node metastasis. We found that tumor thickness was the variable most significantly associated with the probability of nodal metastasis, and the presence of ulceration and tumor location also were significant, but age, sex, and mitotic rate were not. When the resulting logistic model predicted that the probability of nodal metastasis was more than .6, 93 of 115 patients had nodal metastasis. When the model predicted that the probability was less than .3, just 32 of 88 patients had positive nodes. Furthermore, after the result of the node sampling was known, Cox model analysis demonstrated that the pretest probability added significant information about subsequent survival.
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PMID:A model for pretest probability of lymph node metastasis from cutaneous Melanoma. 1133 76

The sentinel lymph node (SN) is the first node on the direct lymphatic drainage pathway from a tumor. Melanoma-associated SNs are the most likely site of early metastases and their immune functions are strikingly down-modulated. We evaluated histologic and cytologic characteristics of 21 SNs and 21 nonsentinel nodes (NSNs) from melanoma patients who had clinically localized (AJCC Stage I--II) primary cutaneous melanoma. SNs showed highly significant reductions in total paracortical area and in the area of the paracortical subsector occupied by dendritic cells. The frequency of paracortical interdigitating dendritic cells (IDCs) was dramatically reduced in SNs, and most IDCs (approximately 99%) lacked the complex dendrites associated with active antigen presentation. The release of immunosuppressive factors from the primary melanoma may induce a localized and specific paralysis in the SN, which prevents the recognition of otherwise immunogenic melanoma antigens by IDCs. This immune paralysis may facilitate the implantation and growth of melanoma cells in the SN. Cytokine therapy may be able to reverse this immune paralysis. These findings have an important practical application in the histopathologic confirmation that a node is truly sentinel. They also offer an hypothesis to explain the failure of the immune surveillance mechanisms to identify and respond to a small primary melanoma that expresses immunogenic tumor antigens.
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PMID:Sentinel lymph nodes show profound downregulation of antigen-presenting cells of the paracortex: implications for tumor biology and treatment. 1140 63

In thin melanomas, the involvement of regional nodes is very uncommon. Recent sentinel node (SN) studies have confirmed the absence of positive regional lymph nodes in melanomas < 0.76 mm and a 5% positivity in melanomas between 1.0 and 1.99 mm. The chance of regional lymph node involvement - and therefore whether it is relevant to perform the SN procedure - seems to depend on the Breslow thickness of the primary tumour. However, a Breslow thickness cut-off point has not yet been established. We evaluated a melanoma population that had undergone an SN procedure to determine this point, so that the procedure can be restricted to a smaller group of patients in future. In a total of 348 patients with proven American Joint Committee on Cancer (AJCC) stages I or II cutaneous melanoma with a Breslow thickness > or = 0.5 mm the triple technique was used, consisting of preoperative visualization of the lymph channels from the initial site of the melanoma towards the SN by (dynamic) lymphoscintigraphy, intraoperative visualization of those particular lymph channels and nodes with blue dye, and a gamma probe to measure accumulated radioactivity in radiolabelled lymph nodes. In melanomas thinner than 0.90 mm, no positive SN was found (95% confidence interval 0-5%). This group consisted of 75 patients (22%), with a median follow-up of 31 months. Our data suggest that this procedure need no longer be indicated for almost a quarter of the patient population, because the cut-off point for nodal involvement appears to be a Breslow thickness of 0.90 mm.
Melanoma Res 2001 Jun
PMID:No indication for performing sentinel node biopsy in melanoma patients with a Breslow thickness of less than 0.9 mm. 1146 20

As with most cancers, the aetiology of human cutaneous melanoma is likely to be multifactorial and to include the accumulation of irreversible alterations in an unknown number of genes. Elucidating this molecular progression necessitates both the identification of genetic perturbations at each clinically relevant stage, and the assessment of their impact on the normal melanocyte. The observation that the epidermal melanocyte, in contrast to metastatic melanoma cells, requires activation of the protein kinase C (PKC) pathway to facilitate growth in vitro indicates that one or more isoforms (or substrates) of this large and complex family of proteins are among those that undergo alteration during the development of malignant melanoma. Consequently, a number of studies have investigated the expression of various PKC family members in both melanocyte and melanoma cell lines, without a consensus of opinion as to which isoforms are of biological significance in melanoma development and progression. The present study involved a comprehensive evaluation of the PKC profile in normal melanocytes and in 16 metastatic melanoma cell lines. The results show that the major difference in isoform expression between epidermal melanocytes and melanoma cells is the loss of PKCbeta protein expression in 90% of melanoma cell lines. Examination of PKCbeta in benign and malignant melanocytic lesions revealed that this protein is either downregulated or absent in both naevi and metastatic melanomas. We conjecture that, although the loss of PKCbeta expression is a common phenomenon in malignant melanocytes, it may be related more to a normal process of melanocytic differentiation than to malignant transformation.
Melanoma Res 2001 Aug
PMID:Loss of expression of protein kinase C beta is a common phenomenon in human malignant melanoma: a result of transformation or differentiation? 1147 24


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