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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The term ocular melanoma refers to a heterogeneous group of cancers of melanocytic origin. The precursor of most cases of conjunctival melanoma is known to ophthalmologists as primary acquired melanosis. This condition passes through well-defined stages of tumor progression. Although tumor progression is not obligatory, as a conjunctival melanocytic lesion acquires new biologic properties it is more likely to progress further. Although junctional nevi are seldom encountered beyond childhood and primary acquired melanosis usually develops in middle-aged individuals, these two conditions may be histologically indistinguishable. Most junctional nevi eventually show evidence of differentiation, whereas nearly half of the cases of primary acquired melanosis with atypia progress to melanoma. Therefore, it is possible that aging may modulate the capability of certain clonal proliferations to differentiate. Uveal melanocytes normally reside in mesenchyme, so that the traditional histologic criterion for establishing the diagnosis of most melanomas--breach of an epithelial basement membrane--does not apply. Because uveal melanomas are not easily accessible to incisional biopsy (without disruption of vision), only two points in the spectrum of tumor progression are defined clinically: nevus and melanoma. Experimental evidence suggests that a spectrum of atypical melanocytic proliferations separates benign nevi from melanomas capable of generating metastases. Unlike conjunctival melanomas that spread first to regional lymph nodes, choroidal and ciliary body melanomas preferentially spread first to the liver and are examples of organ-specific metastases.
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PMID:Tumor progression in ocular melanomas. 844 Sep 16

Overexpression of the p53 gene product has been observed in a high percentage of malignant melanomas. To evaluate the role of this protein in the development of melanoma, we examined p53 expression in benign, premalignant, and malignant melanocytic lesions. Using the antibodies DO-7 and 1801, which recognize both wild-type and most mutant forms of the p53 protein, we analyzed by immunohistochemical staining 26 benign nevi, 34 dysplastic nevi from patients at low risk for the development of melanoma, 22 dysplastic nevi from patients at high risk for the development of melanoma, 61 primary melanomas (including 15 that arose from dysplastic nevi), and 10 metastatic melanomas. Expression of the p53 protein was not observed in any of the benign or dysplastic nevi. Of the primary melanomas only 3 (5%) demonstrated nuclear staining, whereas 70% of the metastatic melanomas showed a positive reaction for p53. These data suggest that overexpression of the p53 gene product is a late event in the progression of melanoma and consequently indicate that expression of this protein cannot be used as a marker to identify patients at high risk for the subsequent development of melanoma.
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PMID:Overexpression of p53 is a late event in the development of malignant melanoma. 848 8

We describe two examples of malignant melanoma that present with clinical and histopathologic characteristics resembling the benign acquired dermal nevus and the spindle and epithelioid cell nevus (Spitz's nevus), respectively. Both lesions were present on the trunk of adult patients. The clinical impression in both cases was dermal nevus. Histopathologically, these lesions were fairly well circumscribed and symmetrical; they exhibited an expansile dermal proliferation of atypical nevomelanocytes in nests and fascicles with only minimal intraepidermal involvement. These lesions which we will designate as "nevoid" melanoma can be misinterpreted as benign nevi because of the absence of prominent intraepidermal pagetoid spread and the pattern of apparent dermal maturation at the base of the tumor associated with a gradual diminution of cell size. These features mimic the maturation phenomena in banal dermal nevi and spindle and epithelioid cell nevi. The differential diagnosis includes other types of melanoma, and various benign entities characterized by a predominantly dermal proliferative process, such as deep penetrating nevus and cellular neurothekeoma. The recognition of nevoid melanoma is critical so that patients with these lesions receive appropriate therapy for malignant melanoma.
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PMID:Melanoma mimicking dermal and Spitz's nevus ("nevoid" melanoma). 851 1

To determine whether loss or inactivation of the putative tumor-suppressor gene, p16, represents an initiating or a secondary event in the progression of human melanoma, we evaluated the status of this gene in early and advanced-stage melanomas of sporadic origin. The results of this analysis revealed p16 deletions in 4/6 primary and 6/14 metastatic melanoma cell lines but not in 3/3 metastatic melanoma specimens. Surprisingly, p16 deletions were also detected in 8/8 benign compound nevi and in 1/3 normal human melanocyte isolates. To investigate whether these deletions in benign and malignant stages of the human melanocytic system were specific for p16, we analysed the same specimens and cell lines for expression of p21, another cyclin-dependent kinase inhibitor and potential tumor suppressor. In contrast to p16, expression of p21 was detected in 3/3 melanocytes, in 3/3 benign nevi, and in greater than 50% of malignant melanoma cell lines and specimens. Finally, because of the recently documented inverse relationship between expression of p16 and pRb protein in a variety of tumor cell lines, we analysed some of the p16-positive and negative melanoma cell lines for the presence of pRb protein. The results demonstrated pRb protein in each of these cell lines. Taken together, although this study revealed deletions of the p16 gene in a significant number of sporadic primary and metastatic melanoma cell lines, they were also detected in benign nevus specimens and in some normal human melanocyte isolates. Thus, these findings cast some doubt on the role of this gene as being causal to the onset and progression of human melanoma, in particular, sporadic melanoma.
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PMID:Differential expression of the cyclin-dependent kinase inhibitors p16 and p21 in the human melanocytic system. 864 98

The human antimelanoma antibody V86 was cloned from a single-chain Fv molecule (scFv) fusion phage library displaying the heavy chain variable domain (VH) and light chain variable domain (VL.) repertoire of a melanoma patient immunized with genetically-modified autologous tumor cells. Previous ELISA tests for binding of the V86 fusion phage to a panel of human metastatic melanoma and carcinoma cell lines and primary cultures of normal melanocytes, endothelial, and fibroblast cells showed that measurable binding occurred only to the melanoma cells. In this communication, the strict specificity of V86 for melanoma cells was confirmed by immunohistochemical staining tests with cultured cells and frozen tissue sections. The V86 fusion phage stained melanoma cell lines but did not stain carcinoma cell lines or cultured normal cells; V86 also stained specifically the melanoma cells in sections of metastatic tissue but did not stain any of the cells in sections from normal skin, lung, and kidney or from metastatic colon and ovarian carcinomas and a benign nevus. An unexpected finding is that V86 contains a complete VH domain but only a short segment of a VL, domain, which terminates before the CDR1 region. This VL deletion resulted from the occurrence in the VL cDNA of a restriction site, which was cleaved during construction of the scFv library. Thus V86 is essentially a VH antibody. The effect of adding a VI. domain to V86 was examined by constructing scFv fusion phage libraries in which V86 was coupled to Vlambda or Vkappa domains from the original scFv library of the melanoma patient and then panning the libraries against melanoma cells to enrich for the highest affinity antibody clones. None of the V86-Vlambda clones showed significant binding to melanoma cells in ELISA tests; although binding occurred with most of the V86-Vkappa clones, it was generally weaker than the binding of V86. These results indicate that most of the VL domains in the original scFv library reduce or eliminate the affinity of V86 for melanoma cells. Accordingly, VH libraries could provide access to anti-tumor antibodies that might not be detected in scFv or Fab libraries because of the incompatibility of most randomly paired VH and VL, domains.
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PMID:A melanoma-specific VH antibody cloned from a fusion phage library of a vaccinated melanoma patient. 869 6

Malignant melanoma (MM) is rare in childhood. We report 24 cases of MM in children 16 years old or less, whose histopathological specimens were referred to our department from 1981 to 1993. In only three cases was the diagnosis of MM made clinically. In some cases histological distinction from benign Spitz naevi was difficult, but other cases were referred because of a reluctance to diagnose MM in a child. One child died of disseminated disease, two developed nodal metastases and two developed local recurrence. Of all the lesions, the one which was considered to show the least difference from a benign naevus histologically occurred in the child who died. Awareness that MM, although rare, does occur in childhood, is vital. However, diagnosis is difficult, both clinically and histopathologically.
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PMID:Malignant melanoma in childhood. 903 18

Fibroblast growth factor 2 (FGF2) has been implicated in the pathogenesis of malignant melanoma (MM), but the role of other FGFs and their receptors (FGFRs) is not elucidated. To determine whether FGF1 and FGFR1 may be involved in MM growth in vivo, we have studied the expression of the FGF1 and FGFR1 genes in 77 fresh MM biopsy samples, using RT-PCR analysis. Samples of benign nevi, normal skin and carcinoma cell lines were included as controls. Using RT-PCR analysis, expression of FGF1 and FGFR1 was observed in 69/77 and 68/77 cases, respectively. Immunohistochemical detection of the FGFR1 protein was positive in reactive stromal cells and at a much lower level in neoplastic cells. In situ hybridization experiments demonstrated FGFR1 mRNA mainly located in the stromal component. Southern blot analysis of genomic DNA prepared from MM tumors did not show any structural alteration of the FGFR1 gene. There was no correlation between FGF1/FGFR1 expression and the usual clinicopathological parameters of MM. We conclude that FGF1 and FGFR1 are frequently co-expressed in MM, a situation that may contribute to aberrant autocrine and paracrine pathways. Due to the absence of correlation with clinico-pathological parameters, this expression cannot be used as a marker of prognosis in the management of MM patients.
Melanoma Res 1996 Jun
PMID:Expression of FGF1 and FGFR1 in human melanoma tissues. 881 25

Integrin alpha 2 beta 1 is a transmembrane protein receptor for collagen and laminin previously reported as a melanoma tumor progression antigen. alpha-Actinin is an actin-binding protein reported to interact with the cytoplasmic domain of the beta 1-integrin chain of alpha 2 beta 1. In vitro, both alpha 2 beta 1 and alpha-actinin play a role in melanoma cell motility. In turn, increased melanoma cell line motility (measured as mean migration rates), correlates with metastasis. To determine the in situ distribution of these proteins, we used monoclonal antibodies directed against the alpha 2-integrin subunit of alpha 2 beta 1 and alpha-actinin on frozen sections of 33 melanocytic proliferations, which included dermal nevi, primary melanomas, and metastatic melanomas. We found that the superficial portion of all of the melanocytic proliferations tested stained for alpha-actinin. In benign nevi and superficial spreading melanoma, there was a notable loss of staining for alpha-actinin in the cells in the deep reticular dermis. In contrast, alpha-actinin was present on almost all of the tumor cells in the nodular melanomas and the melanoma metastases. Tumors stained either uniformly positive or uniformly negative for alpha 2 beta 1; the expression of this protein correlated with the later stages of melanoma progression. Our findings suggest that alpha-actinin protein levels initially decrease and then increase during melanocytic tumor progression, whereas the alpha 2 subunit protein appears in the later stages of melanoma progression. The variable distribution of these proteins is evidence for the differential adhesive and motile properties of subpopulations of cells in melanocytic proliferations.
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PMID:In situ distribution of integrin alpha 2 beta 1 and alpha-actinin in melanocytic proliferations. 887 27

Malignant melanoma may originate from melanocytes in ovarian cystic teratomas (dermoid cysts). Two cases are reported here and an additional 17 cases are found in a literature review covering 1903-1995. The review also found cases of benign and malignant melanotic ovarian lesion unassociated with dermoid cyst, including four melanomas, three cases of benign nevus, five cases of benign melanosis, and four cases of benign and malignant retinal anlage tumors. The extremely rare primary ovarian melanoma may be differentiated from the more common melanoma metastatic to the ovaries by its unilaterality, the presence of junctional change, and a detailed history and physical examination to exclude another primary site. Overall, 50% of patients with Stage I dermoid-associated melanoma were alive at 2 years compared with 89% of patients with Stage I dermoid-associated squamous carcinoma at 5 years. In the last 10 years, however, with the application o aggressive chemotherapy, survival has improved.
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PMID:Malignant melanoma arising in mature ovarian cystic teratoma (dermoid cyst). Report of two cases and literature analysis. 888 84

The purpose of this study was to evaluate whether or not, using sensitive analytical methods for the measurement of coagulation and fibrinolysis enzyme activity, there was a hypercoagulable state in patients with melanoma, and whether differences existed between those with or without metastases. Seventy-one patients were studied, 45 with localized tumors (stages Ia and Ib) and 26 with metastases (stages II-IV). Plasma level of activated factor VII, prothrombin fragment 1 + 2, thrombin-antithrombin complex, fibrinopeptide A, plasmin-antiplasmin complex and D-dimer were much higher in the whole group of 71 patients than in 45 controls with benign nevi. However, when melanoma patients with or without metastases were compared, there were smaller differences, with only thrombin-antithrombin complex, plasmin-antiplasmin and D-dimer significantly higher in metastatic melanoma. These results indicate that in patients carrying a tumor endowed with high procoagulant activity in vitro, there is a laboratory picture of hypercoagulability with secondary hyperfibrinolysis in vivo. However, differences between patients with localized and metastatic tumors for markers of hypercoagulability are not striking, in spite of the fact that metastatic cells support greater coagulant activity than primary cells in vitro.
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PMID:Hypercoagulability and hyperfibrinolysis in patients with melanoma. 892 92


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