Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The reactivity of four monoclonal antibodies (MAbs) directed against IFN-gamma inducible antigens with melanocytic cells was investigated in the course of local and systemic tumor progression of human malignant melanoma. Frozen sections of histologically defined melanocytic tissues at different stages of progression were stained with these MAbs using an indirect immunoperoxidase technique. The reactivity of MAbs Me15/B3 and Me15/F9, directed against two different epitopes of a 90-kDa molecule, was found to correlate with melanoma progression. Indeed, a significantly lower percentage of small than of advanced primary melanomas or metastases stained positively. A differential staining of nevocytic and dysplastic nevi was further observed for these two MAbs, which were also non-reactive with normal skin melanocytes. The reactivity of MAb Me14/D12, which identifies the intercellular adhesion molecule ICAM-1 and MAb Mel14/F12, directed against a 40-kDa molecule, was found to be independent of the Breslow thickness of primary melanomas. Both the latter MAbs stained a high proportion of nevocytic and dysplastic nevi. The co-expression of the surface molecules defined by MAbs Me14/D12, Me15/B3 and Me15/F9 in the course of melanoma progression was also analyzed. The frequency of this co-expression increased according to the Breslow thickness of primary melanomas. In addition, up to 100% of metastases, as opposed to 20% of dysplastic nevi, were found to be simultaneously stained by these three MAbs. It is therefore conceivable that high-risk melanocytic lesions might be identified by the use of a combination of MAbs directed against IFN-gamma regulated antigens.
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PMID:The differential reactivity of cells of the melanocytic lineage with four monoclonal antibodies against IFN-gamma inducible molecules. 134 19

Different results have been reported on the expression of epidermal growth factor receptor (EGFR) in human melanocytic lesions, which may be due to different methodologic approaches. Therefore, we compared EGFR expression in six human melanoma cell lines by utilizing the monoclonal antibodies 2E9, 425, and 225, applying four immunocytochemical staining procedures. The results were compared with those obtained by a multiple point ligand binding assay. In addition, Northern blot analysis was performed. A three-step immunoperoxidase method using the monoclonal antibody 2E9 proved most sensitive. Staining intensities, estimated semiquantitatively, correlated well with the quantitative data obtained by the ligand-binding assay. Expression on the mRNA level was also in agreement with these results. Immunohistochemical staining of a large series of human cutaneous melanocytic lesions using the method selected showed differential EGFR expression in various stages of melanocytic tumor progression: 19% of common nevocellular nevi; 61% of dysplastic nevi, 89% of primary cutaneous melanomas, and 91% of melanoma metastases showed staining of the melanocytic cells. Intralesional heterogeneity of EGFR expression was present. Although the mean percentage of positive melanocytic cells in positive lesions did not increase with progression, mean staining intensity was stronger in malignant lesions compared to benign lesions. Ligand binding assays showed that EGFR expression in the highly metastasizing cell lines MV3 and BLM was at least 40 times higher than in the cell lines IF6, 530, M14, and Mel57, which do not or only sporadically metastasize after subcutaneous inoculation in nude mice. Although the differences between the various stages of progression are not absolute, we provide further evidence that EGFR expression increases in human melanocytic tumor progression.
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PMID:Increasing epidermal growth factor receptor expression in human melanocytic tumor progression. 162 28

Three malignant melanomas, two melanoma metastases, two junctional dysplastic nevi, and normal skin were embedded in Lowicryl. Ultrathin sections were incubated with HMB-45 and a gold-labeled anti-mouse antibody. Gold particles indicating the presence of HMB-45 were found in melanosomes Stage 1 and 2 and in the non-melanized portion of melanosomes Stage 3. Melanosomes Stage 4 and melanosome complexes in keratinocytes, as well as in melanophages, were consistently negative. No specific labelling with HMB-45 was seen in eccrine glands of normal skin.
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PMID:Ultrastructural localization of HMB-45 binding sites. 177 53

Malignant melanoma is increasing in frequency and is becoming one of the leading causes of cancer death. Early recognition and treatment is often curative. Recognition includes the identification of malignant precursors, the dysplastic nevus. Prognosis for survival and disease is dependent upon tumor thickness, level of invasion, anatomic location, growth pattern, ulceration as well as age and sex. Adequate biopsy of suspicious lesions is critical to both diagnosis and prognosis. Wide excision is the treatment of choice, with margins determined by tumor thickness. The management of regional lymph nodes remains controversial. Radical lymphadenectomy is indicated for clinically suspect adenopathy and may improve survival. There does not appear to be significant benefit of elective lymph node dissection for melanomas less than 0.76 mm or greater than 4 mm in thickness. Intermediate lesions may be managed in one of two ways: through careful follow-up with node dissection performed if clinical change is evident; or ELND may be performed. Ongoing trials to determine the benefit of ELND are presently under way. Isolated limb perfusion may be a desirable option for adjuvant therapy in the treatment of extremity melanomas, especially in patients with high-risk lesions or with disease recurrence since improved survival may be achieved. The role of surgical intervention in the management of distant metastases is limited but may have a role in palliation.
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PMID:Malignant melanoma: current management. 233 75

We have used polymerase chain reaction (PCR), an amplification procedure, and oligonucleotide hybridization to detect ras gene point mutations in DNA from melanoma tumor samples. Genomic DNA was examined from 40 specimens of melanotic lesions, including benign nevi, primary melanomas, lymph node metastases, and systemic metastases. Adjacent normal skin or peripheral blood was analyzed as control material in 28 cases. ras mutations were detected overall in 25% of malignant tumors. In addition, mutations of all three ras genes were detected. We observed ras mutations in 2 of 4 benign atypical nevi (2 X K12), 4 of 22 primary melanomas (3 X K12, 1 X H12, 1 X N61), and 4 of 14 secondary (5 X K12, 1 X N61) tumors. One with a primary melanoma had concurrent K12 and H12, and two patients with secondary tumors had concurrent K12/N61 and K12 Asp/K12 Val mutations, respectively, making a total of 10 of 40 (25%) patients with ras mutations. This is the first demonstration of K-ras mutations in human melanoma. The presence of K-ras mutations in nevi, putative melanoma precursors, suggests that ras activation may be an early event in melanoma development. No correlation between tumor thickness and the presence of a ras mutation was observed.
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PMID:ras mutations in human melanotic lesions: K-ras activation is a frequent and early event in melanoma development. 269 57

The gene for familial malignant melanoma and its precursor lesion, the dysplastic nevus, has been assigned to a region of the distal short arm of chromosome 1, which is frequently involved in karyotypic abnormalities in melanoma cells. We have examined loci on chromosome 1p for loss-of-constitutional heterozygosity in 35 melanomas and 21 melanoma cell lines to analyze the role of these abnormalities in melanocyte transformation. Loss-of-heterozygosity at loci on chromosome 1p was identified in 15/35 (43%) melanomas and 11/21 (52%) melanoma cell lines. Analysis of multiple metastases derived from the same patient and of melanoma and lymphoblastoid samples from a family with hereditary melanoma showed that the loss-of-heterozygosity at loci on distal 1p is a late event in tumor progression, rather than the second mutation that would occur if melanoma were due to a cellular recessive mechanism. Comparisons with neuroblastoma and multiple endocrine neoplasia (MEN2) suggest that the frequent 1p loss-of-heterozygosity in these malignancies is a common late event of neuroectodermal tumor progression.
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PMID:Loss of alleles from the distal short arm of chromosome 1 occurs late in melanoma tumor progression. 273 11

It has been proposed that the pathogenesis of melanoma proceeds through multiple stages, ranging from benign proliferation of melanocytic cells to acquisition of the capacity to invade tissues and metastasize. During investigations of cell surface antigens expressed by melanocytes and melanoma, we identified an antigen system that was expressed by cultured normal melanocytes but not by melanoma cell lines. mAbs against this antigen detected a 120-kD cell surface glycoprotein on melanocytes. This molecule had been identified previously as the binding protein for adenosine deaminase (ADAbp). ADAbp was expressed by 51 melanocyte cell lines derived from normal fetal, newborn, and adult skin and adult choroid, but not by 102 melanoma cell lines derived from primary and metastatic lesions. Studies with radiolabeled bovine adenosine deaminase, confirmed that melanocytes expressed binding sites for adenosine deaminase, but no binding sites were detected on cultured melanoma cells. Further studies showed that ADAbp+ melanocytes became ADAbp- upon malignant transformation in vitro. Immunohistochemical studies on a panel of frozen tissues demonstrated reactivity of anti-ADAbp mAbs with epidermal melanocytes and benign junctional nevi, but not with potentially premalignant dysplastic nevi or primary/metastatic melanoma lesions. These studies demonstrate that ADAbp expression is lost with malignant transformation of melanocytes, presumably at an early stage in the transformation process.
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PMID:Cell surface antigens of human melanocytes and melanoma. Expression of adenosine deaminase binding protein is extinguished with melanocyte transformation. 289 80

To determine whether plasma 5-S-cysteinyldopa levels are useful in following up patients at risk for melanoma, we measured plasma 5-S-cysteinyldopa in patients with dysplastic nevus syndrome and/or malignant melanoma and in control subjects. In patients with dysplastic nevus syndrome, plasma 5-S-cysteinyldopa levels did not differ from those in control subjects. Conversely, patients with malignant melanomas had significantly higher plasma 5-S-cysteinyldopa levels than did controls. Those with localized cutaneous malignant melanoma and no distant metastases (Stage I and II disease) had 5-S-cysteinyldopa levels twofold greater than those of control subjects, whereas the levels of those with regional lymph node involvement (Stage III disease) were fourfold greater than those of control subjects. Levels of those with extraregional metastases (Stage IV disease) were 7- to 450-fold higher than those of control subjects. Moreover, plasma 5-S-cysteinyldopa levels correlated with the spread of disease and were useful in distinguishing primary melanoma and Stages III and IV melanoma. We conclude that plasma 5-S-cysteinyldopa may be an important tool for identifying melanoma at an earlier, more curable stage and for following up patients at risk for the development of melanoma, for example, those with dysplastic nervus syndrome.
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PMID:Plasma 5-S-cysteinyldopa differentiates patients with primary and metastatic melanoma from patients with dysplastic nevus syndrome and normal subjects. 313 23

Fifty-six formalin, Bouin's, and Carnoy's fixed, paraffin-embedded malignant melanomas (21 primary, 35 secondary), were studied by avidin-biotin complex immunohistochemistry using monoclonal antibodies (MoAb) HMB-45 and B1.1, comparing reactivity with polyclonal anti-S-100 protein. B1.1 (anti-CEA MoAb) was expressed in a minor percentage of cells of the invasive component of some primary melanomas, and weak to moderately in scattered metastic melanoma cells. MoAb HMB-45 prepared against melanocytic tumors reacted with over 90% of all tumors studied, being weakly reactive in one, and nonreactive in four metastases. This antibody stained some primary melanomas and their dysplastic nevus components in a heterogeneous manner, but was largely nonreactive in deep dermal nevus cells that were in association with invasive melanoma, enabling recognition of the deepest penetration of melanoma cells in the dermal nevus component. MoAb HMB-45 appears specific for melanoma cells, with no cross-reactivity with nonnevomelanocytic malignant tumors (unlike polyclonal anti-S-100 protein). MoAb HMB-45 is more sensitive in detecting malignant melanoma cell heterogeneity than anti-S-100 protein.
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PMID:Melanoma cell heterogeneity. A study of two monoclonal antibodies compared with S-100 protein in paraffin sections. 336 69

The retinoids have been investigated extensively as chemopreventive and therapeutic agents in a variety of neoplasms. They have been shown to inhibit the proliferation of transformed cell lines in vitro and transplanted tumors in vivo. In cultured murine melanoma cells, retinoids inhibit proliferation and induce differentiation. Human melanoma cell lines have shown a mixed response. The clinical experience with retinoids in melanoma has been limited. Previously we investigated the activity of topical B-all-trans-retinoic acid (Retin-A, vitamin A acid, retinoic acid, and tretinoin) against intracutaneous metastases from malignant melanoma. We saw complete remission of multiple lesions in one individual and regression of several lesions in a second patient. This experience led us to conduct the present pilot trial of topical tretinoin in dysplastic nevus syndrome. The latter is a precursor of malignant melanoma. We saw regression of some of the treated lesions to benign nevi showing minimal or no dysplasia. Thus topical tretinoin appears to possess some activity against melanoma and at least one of its precursor conditions. In view of these preliminary results, more extensive trials are warranted to better define the role of tretinoin in the chemoprevention of malignant melanoma in high-risk lesions.
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PMID:Role of topical tretinoin in melanoma and dysplastic nevi. 353 20


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