Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunohistochemical analysis of the expression of the cyclin kinase inhibitor p21WAF1/CIP1 in a panel of primary and metastatic human melanocytic tumors was performed. It was found that, independent of the p53 status, approximately 30% of the primary melanomas and 40% of the metastases completely lacked expression of this cell cycle inhibitor. Some tumors were also analyzed by Northern blotting, and in most of the cases a consistant correlation between mRNA and protein expression was observed. In four benign nevi studied, WAF1/CIP1 mRNA was expressed whereas the protein was not detected, suggesting a post-transcriptional regulation of the inhibitor in these cases. In superficial spreading melanomas, a significant correlation between protein expression and tumor thickness was found, with thin lesions showing low protein levels. Interestingly, by comparing primary and metastatic specimens obtained from the same patient, a reduction in p21WAF1/CIP1 antibody staining was observed in the latter, probably reflecting a more aggressive phenotype of the metastases. In conclusion, our results demonstrate the complexity in the relationship between p21WAF1/CIP1 expression and tumor phenotype and furthermore suggest that aberrant expression of the cyclin-dependent kinase inhibitor may be of importance in the development and progression of sporadic malignant melanoma.
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PMID:Cyclin kinase inhibitor p21WAF1/CIP1 in malignant melanoma: reduced expression in metastatic lesions. 895 18

CD40 is a receptor at the surface of B lymphocytes with important functions in the immune response. CD40 has also been found on a variety of carcinoma and melanoma cell lines where it has been suggested to serve as a possible receptor for mitogenic signals. We studied the expression and distribution of CD40 in paraffin sections of 71 uniformly treated malignant melanomas (MMs) with a long clinical follow-up using well known monoclonal antibodies. For comparison, 71 benign nevi were also studied. Common acquired nevi occasionally expressed CD40 in nests or single cells at the dermo-epidermal junction; no immunoreactivity was observed in the dermal part of acquired nevi, and all Spitz' nevi were entirely negative. One-third of large congenital nevi expressed CD40 in small clusters of heavily pigmented, epithelioid cells, corresponding to so-called proliferative nodules. In 41 of 71 MMs, CD40 was expressed in single or clustered neoplastic melanocytes; 9 cases showed CD40 expression only in the radial growth phase, and in 32 cases, the vertical growth phase showed CD40 expression. The same staining pattern was obtained with other anti-CD40 monoclonal antibodies, directed to different epitopes of the CD40 molecule. In 29 of 32 MMs showing CD40 in the vertical growth phase, expression of the CD40 ligand (CD40L) was studied; in 13 of these 29, CD40L was found in the same tumor areas that expressed CD40. Analysis of 28 metastases from 24 MM patients showed in the majority of cases a similar, scattered or nodular staining pattern as observed in the primary tumor. Patients expressing CD40 in the vertical growth phase of their MM did not differ significantly from CD40-negative patients with respect to any of the known prognostic parameters but showed a significantly shorter tumor-free survival. Patients with CD40+ CD40L+ MM tended to have a shorter tumor-free survival than those lacking CD40L. We conclude that CD40 represents a novel prognostic parameter in primary cutaneous MM. The co-localization of CD40 and CD40L suggests an autocrine growth loop in the vertical growth phase of MM.
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PMID:CD40 is a prognostic marker in primary cutaneous malignant melanoma. 895 30

Atypical (dysplastic) nevi are melanocytic lesions, which are precursors of melanoma as well as markers of increased melanoma risk. Although these lesions exhibit distinct clinical and histological features, their molecular features are largely unknown. To determine whether atypical, compared to benign nevi, from patients with a clinical history of malignant melanoma reveal molecular changes, we analyzed these lesions for the expression of two growth factors (basic fibroblast growth factor and transforming growth factor alpha), their receptors (fibroblast growth factor receptor-1 and epidermal growth factor receptor), and two cell adhesion molecules (MUC18 and alpha v beta 3 integrin), all of which are expressed in primary and metastatic melanomas. The results demonstrated a statistically significant correlation (P = 0.02) between increasing degrees of histological atypia and expression of epidermal growth factor receptor in the epidermal keratinocytes of atypical melanocytic lesions. Furthermore, both atypical and benign nevi revealed considerably high levels of overall gene activity in their dermal melanocytic and epidermal keratinocytic compartments. In contrast, the epidermal-dermal junction wherein melanoma evolves showed little gene activity, suggesting that molecular events occurring adjacent to this junction may be important for melanocytic transformation.
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PMID:Molecular analysis of melanoma precursor lesions. 895 42

The diagnosis of malignant melanoma requires clinical recognition of suspect lesions, biopsy, and histologic examination. Histological features which serve to distinguish malignant melanoma from their benign counterparts can be found in both the epidermis and dermis. The intraepidermal component of a common acquired nevus usually consists of more or less uniform theques of melanocytes located at or near the tips of rete ridges. Most melanomas are characterized by less orderly intraepidermal growth with areas in which melanocytes lose their nesting characteristics and are distributed more diffusely, sometimes replacing the basal keratinocytes by confluent growth and sometimes by invading upwards either as single cells or small nests into the upper reaches of the epidermis. Nested melanocytes can be found along the basal layer in malignant melanoma, but these nests are usually quite variable in size and location with respect to the tips of the rete ridges, and they are often irregularly distributed along the breadth of the lesion. The dermal component of malignant melanoma usually shows little tendency towards maturation, unlike that of benign nevi. Mitotic figures are unusual to find in the dermal component of common acquired nevi. When they are present, the possibility of melanoma should be considered. Other cytological features can also be useful in the diagnosis of malignant melanoma, particularly when there is marked cytological atypia; however, in some lesions, the cytological changes are not so pronounced and correct diagnosis depends on evaluation of growth pattern. While distinguishing between melanoma and atypical moles can be difficult, problems also arise in distinguishing melanoma from other neoplastic processes. The most common differential diagnosis includes melanoma, paget's disease, and pagetoid Bowen's disease. Desmoplastic melanoma is frequently difficult to distinguish from spindle cell squamous cell carcinoma and atypical fibroxanthoma. Histochemical and immunocytochemical stains are useful in resolving these problems. The pathology report of a melanoma should include the diagnosis, the maximum thickness of the tumor, the adequacy of the surgical margins (if the lesion has been excised), the presence or absence of ulceration, tumor regression, angiolymphatic invasion, and satellitosis. The inclusion of patients in treatment protocols may require additional information such as the host response of tumor-infiltrating lymphocytes, mitotic index, and Clark's level of invasion.
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PMID:Melanoma: criteria for histological diagnosis and its reporting. 897 May 88

Two cases of malignant melanoma arising in established stasis dermatitis are described. One case was clinically thought to be melanocytic whereas the other was not. Histologically, both showed similar features with background varicose change of epidermal atrophy, sloughing of the epidermis, intense proliferation of small thick walled blood vessels, lymphocytic infiltrate and dermal fibrosis. In the superficial aspects of the biopsies there was little clue to the diagnosis of melanoma. In the deeper aspects of case 1, groups of melanocytes were present in the reticular dermis which mimicked benign naevus cells. S-100 protein staining confirmed the melanocytic nature of these lesions, their extent and the epidermal involvement. The latter features supported a malignant diagnosis. These lesions can be overlooked clinically as well as histologically.
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PMID:Malignant melanoma in stasis dermatitis. 906 37

An appropriate biopsy is the pivotal procedure that facilitates accurate histopathologic diagnosis of a pigmented skin lesion. Excisional skin biopsy is the method of choice for removing a suspected malignant melanoma. More than 95% of malignant melanomas that involve the skin belong to one of the four most common clinicopathologic categories: superficial spreading, nodular, lentigo maligna, and acral lentiginous melanoma. A small but important group of cutaneous melanomas can be classified as unusual variants. Many of these unusual variants have a distinct histopathologic appearance; they include desmoplastic melanoma, neurotropic melanoma, pedunculated melanoma, metastatic melanoma, amelanotic melanoma, melanoma arising within a benign nevus, regressing ("invisible") melanoma, and balloon cell melanoma. Other lesions may simulate malignant melanoma histopathologically. Immunohistochemical stains, such as S-100 protein, vimentin, keratin, and HMB-45, are useful for distinguishing these lesions from true melanoma.
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PMID:Dermatopathologic variants of malignant melanoma. 907 Feb 5

During progression from benign nevus to vertical growth phase melanoma, melanocytes acquire the ability to invade into the dermis. This process requires rupture of the basal lamina and dissolution of dermal type I collagen. Metastases-derived human melanoma MIM cells have an invasive ability in vitro which is dependent on metalloproteinases. In the present study we analysed the role of type I collagenase (MMP-1) in melanoma invasion using MIM cells in which the constitutive expression of MMP-1 was suppressed by stable transfection with a plasmid vector expressing a 777 bp antisense fragment of MMP-1 genomic DNA. Two clones were isolated in which MMP-1 mRNA expression was blocked by 90-96% with a corresponding loss in protein synthesis. In their morphological appearance and growth rate in vitro these cells were indistinguishable from wild type cells or control cells transfected with the same vector expressing the MMP-1 fragment in the sense orientation. Their mRNA and protein levels for type IV collagenase (MMP-2) were unchanged as assessed by Northern and Western blot analyses and by gelatin zymography. However, when the invasive ability of the cells was measured, we found that in addition to type I collagen, invasion through type IV collagen and a reconstituted, type IV collagen-containing basement membrane (Matrigel) were also significantly inhibited as compared to normal or sense-transfected cells. The results indicate that despite the presence of functional MMP-2, degradation of type IV collagen matrices by the melanoma cells was dependent on expression of MMP-1.
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PMID:Suppression of basement membrane type IV collagen degradation and cell invasion in human melanoma cells expressing an antisense RNA for MMP-1. 919 70

p21(WAF1/CIP1) (p21) is an inhibitor of cyclin-dependent kinases recently identified as the downstream effector of wild-type p53-mediated cell cycle arrest. The gene coding for p21 may function as a negative regulator of melanoma growth, progression, and metastasis. Using immunohistochemistry and Western blotting, we investigated the expression of p21 in human melanocytic proliferations. Immunohistochemical staining was performed on 13 common acquired nevi, 12 dysplastic nevi, 23 primary malignant melanomas, and 12 metastatic melanomas. Common acquired nevi showed minimal p21 staining (1.8+/-0.3%, mean+/-SEM). The percentage of positive nuclei was slightly elevated in dysplastic nevi (8.9+/-1.7%). Both primary malignant melanoma (29+/-3%) and metastatic melanoma (33+/-5%) demonstrated a significantly increased number of p21-positive nuclei compared to benign lesions (p<0.001). p21 was strongly expressed even in actively proliferating lesions as confirmed by MIB-1 labelling, and although the majority of p21-positive cells likely represent a non-proliferating population, staining was occasionally observed in cells undergoing mitosis, suggesting abnormal function of this cell cycle inhibitor in malignant melanoma. Overexpression of p21 in metastatic melanoma compared to common acquired nevi was confirmed by Western blot analysis of human tumor samples. These findings suggest that increased p21 expression relative to benign nevi is not sufficient to control melanoma growth in vivo.
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PMID:Overexpression of the cyclin-dependent kinase inhibitor p21(WAF1/CIP1) in human cutaneous malignant melanoma. 919 78

Three members of the S100 gene family, S100A2, S100A4 and S100A6, have been suggested to be associated with cancer development and metastasis. To study their involvement in the tumorigenesis of human melanoma, we examined the mRNA expression levels of the 3 genes in 45 melanoma metastases and in 20 benign nevi. Interestingly, whereas none of the metastases expressed S100A2 mRNA, and the expression level was low in 6 cell lines established from primary melanomas, all nevi showed moderate to high expression levels. Our results suggest that loss of S100A2 gene expression may be an early event in melanoma development. A significant correlation was found between the expression of S100A6 in melanoma metastases and both the survival time of the patients and the thickness of the corresponding primary tumors. For the S100A4 gene, however, no relationship was found between gene expression and clinical parameters of melanoma malignancy. The observed differences in expression patterns of the 3 S100 genes suggest distinct roles of their products in melanoma tumorigenesis and/or metastasis, and the results encourage studies to evaluate the potential value of using S100A2 and S100A6 expression levels as markers in the clinical management of melanoma.
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PMID:Differential expression patterns of S100A2, S100A4 and S100A6 during progression of human malignant melanoma. 929 41

The c-kit gene encodes a transmembrane receptor that has tyrosine kinase activity. c-kit plays a role in hematopoiesis, gametogenesis, and melanogenesis. c-kit is found in melanocytes, and there is evidence that expression is lost in melanoma. We studied 85 melanocytic lesions for c-kit by immunohistochemical techniques using a monoclonal antibody. The lesions included banal nevi, junctional and compound nevi with melanocytic dysplasia, nontumorigenic radial growth phase melanoma, tumorigenic vertical growth phase melanoma, and metastatic melanoma. We found intense membrane staining in normal melanocytes and mast cells. Staining in compound nevi was strongest in junctional and superficial dermal components, whereas dermal nevi showed weak reactivity. Dysplastic nevi stained strongly, particularly in junctional cells. In melanoma, strong reactivity was most prominent in radial growth phase disease, but there was little or no staining in vertical growth phase and metastatic melanomas. In summary, c-kit protein is expressed in normal melanocytes, benign nevi, dysplastic nevi and nontumorigenic melanoma, but expression is lost in tumorigenic primary melanomas and metastases. The role of c-kit loss in advanced melanoma requires additional investigation.
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PMID:Proto-oncogene c-kit expression in malignant melanoma: protein loss with tumor progression. 931 Sep 59


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