Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The intracellular localization of antigenic sites recognized by the monoclonal antibody HMB-45 was investigated in melanomas of the choroid and skin by postembedding immunoelectron microscopy. Antigenic sites were detected by a three-step procedure, consisting of incubating sections with the monoclonal HMB-45 antibody (protein G affinity-purified ascites from Enzo Diagnostics Inc or tissue culture supernatant from Dako Corp), followed by incubation with an affinity-purified rabbit anti-mouse IgG and finally with protein A-gold complex. Gold particles, indicative of HMB-45 immunoreactivity, were restricted to melanosomes in the malignant melanocytes. Early stages in melanosome formation (stages I through III) were most intensely stained, while late-stage melanosomes (stage IV) were only sparsely labeled or not stained at all. Melanophages adjacent to a cutaneous melanoma showed intense immunoreactivity in the cytoplasm and especially over electron-dense portions of lysosomes with the HMB-45 antibody from Enzo. In marked contrast, only very sparse labeling was detected over melanophages using a similar concentration of the HMB-45 antibody from Dako. Subsequently, when the Enzo antibody was diluted 40 times above the recommended working dilution, most of the melanophage staining disappeared, while melanocyte-specific staining was maintained. Immunolabeling of melanosomes with HMB-45 was drastically reduced or absent following section pretreatment with neuraminidase, confirming an earlier report that the HMB-45 antigen is partially composed of sialic acid. Our immunoelectron microscopic results show that HMB-45 antibody specifically stains melanosomes, rather than diffuse cytoplasmic antigen, as described by light microscopic immunohistochemical analysis, thus explaining its specificity for melanocytes. In addition, the elimination of HMB-45 immunoreactivity by neuraminidase pretreatment supports the idea that sialylation of antigen is crucial to HMB-45 binding, and suggests that the absence of staining in normal adult melanocytes, dermal nevi, and other melanocytic lesions may be a result of differential sialylation.
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PMID:HMB-45 antibody demonstrates melanosome specificity by immunoelectron microscopy. 844 72

Cutaneous malignant melanoma and its precursors were the general subjects of the National Institutes of Health Consensus Conference held in January 1992. Particular emphasis was placed on the diagnosis of early melanoma, especially melanoma in situ, and the controversies surrounding dysplastic nevi. Recent studies of unusual nevi often confused with melanoma, eg, deep-penetrating (plexiform) nevus, combined nevus, desmoplastic melanocytic nevus, and Spitz nevus in childhood, provided detailed histologic criteria for their discrimination from melanoma. Rare or unusual forms of melanoma, including desmoplastic melanoma, neurotropic melanoma, a newly described variant angiotrophic melanoma, subungual melanoma, and balloon cell melanoma have been the subject of comprehensive histologic studies. Other histopathologic investigations have described the prevalence of histologic regression and intraepidermal pagetoid spread in melanomas and the histologic features of reexcision specimens of melanoma. New evidence suggests that the predominant cell type infiltrating melanoma is the monocyte-macrophage, and the expression of monocyte chemotactic protein-1 by melanoma may explain the recruitment of this cell type. Immunopathologic studies of melanocytic lesions were performed with various melanocyte-associated antigens (eg, HMB-45), proliferation antigens (eg, Ki-67), and progression markers (eg, epidermal growth factor receptor and HLA-DR). HMB-45 binding has been localized ultrastructurally to early melanosome formation. Various prognostic factors, including gender, high-risk anatomic sites (particularly the scalp), race (black vs white patients), microscopic satellites, tumor volume, indices of proliferation and tumor cell motility, volume-weighted mean nuclear volume, DNA ploidy, and nucleolar organizer regions have been the subject of recent investigations. Analysis of many patients with long-term follow-up has facilitated better prognostic modeling of melanoma.
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PMID:Pathology and prognostic factors. 845 20

The aim of the present study was to evaluate the frequency with which histologically confirmed dysplastic nevi are observed among patients with superficial spreading melanoma compared to patients with nodular melanoma. A pathology review of 117 new cases of first primary nonfamilial cutaneous melanoma identified 61 patients with superficial spreading melanoma and 19 with nodular melanoma. Study participants received a physician-conducted skin examination which included enumeration of clinically benign and atypical nevi and the surgical excision of the clinically most atypical nevus. Patients' dysplastic nevus status was established by histological review of the clinically most atypical nevus. A comparison based on the tumor subtypes showed that dysplastic nevi occur nearly four times more frequently among patients with a prior diagnosis of superficial spreading melanoma relative to nodular melanoma (odds ratio = 3.6; P = 0.03).
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PMID:Dysplastic nevi in relation to superficial spreading melanoma. 846 53

The dysplastic nevus syndrome was conceptualized in the late 1970s, and the subsequent proposal of a genetic relationship with ocular melanoma has stimulated debate in the literature which remains unresolved. We present the case of a 60-year-old man with histologically proven sporadic dysplasic nevus syndrome and a prior history of nine cutaneous melanomas, who developed a large, exophytic melanoma of the cornea and limbal conjunctiva. Cytogenetic analysis of this melanoma revealed a clonal 1;14 translocation. We believe this is the first reported case to use cytogenetic techniques in the analysis of conjunctival melanoma, either associated with dysplastic nevus syndrome or in isolation. We review the clinical literature as well as the cytogenetic and molecular genetic data related to the possible association of cutaneous melanoma, conjunctival and uveal melanoma and the dysplastic nevus syndrome.
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PMID:Conjunctival and uveal melanoma in the dysplastic nevus syndrome. 848 71

Cutaneous nevi are common lesions that develop by proliferation of melanocyte-derived cells. The majority develop as junction nevi from melanocytes at the epidermo-dermal junction. Cells from this proliferation pass into the underlying dermis forming compound nevi. Later junctional melanocytic activity ceases, leaving an intradermal nevus. A minority of nevi, mainly blue nevi, arise from intradermal melanocytes. Histological variants of melanocytic nevi exist and can be the source of difficult diagnostic problems. Nevi are important as clinical and histological simulators of cutaneous melanoma, as precursor lesions for melanoma (although the actual chance of malignant transformation of an individual nevus is low) and as cosmetic problems (mainly large congenital nevi). Cutaneous nevi are to be separated clinically and histologically from melanomas that are comprised of nevocyte-like cells (minimal deviation melanoma).
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PMID:Nevi, other than dysplastic and Spitz nevi. 850 15

Alterations in the tumor-suppressor gene p53 are common in many types of human malignancies, but the potential role of p53 in the pathogenesis of cutaneous melanoma is controversial. The gene product, p53 protein, is normally present in very small amounts in noncancerous tissues. Missense mutations lead to accumulation of mutant p53 in the cells, which makes it detectable immunohistochemically in many cancers. Formalin-fixed, paraffin-embedded sections of 14 primary invasive melanomas, 3 cutaneous melanoma metastases, and 10 predominantly intradermal melanocytic nevi were reacted with a panel of three anti-p53 monoclonal antibodies (mAbs) (PAb240, PAb1801, and DO7) and a mAb against Ki-67 (MIB-1), a marker of cellular proliferation. p53 was not detected in morphologically normal epidermal melanocytes or nevus cells. A single primary invasive melanoma, having a very high index of proliferation (Ki-67 expression in > 50% of cells), had diffuse nuclear labeling with all three anti-p53 mAbs used. Abnormalities of p53 expression occur rarely in cutaneous melanomas, but overexpression of p53 may occur in a subset of melanomas with a high index of proliferation.
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PMID:p53 expression is rare in cutaneous melanomas. 860 Jul 97

An analysis of the relationship between the anatomic site of cutaneous melanoma, sun exposure, and phenotype was conducted in 355 women with histologically confirmed superficial-spreading melanoma and in 935 control subjects. The most frequent site for superficial-spreading melanoma was the leg. However, when major sun-related and phenotype risk factors were examined by site, risk ratios were lowest for melanomas that occurred on the leg. A history of frequent sunburns during elementary or high school, increased number of self-assessed large nevi, and blond hair were more strongly associated with melanoma sites other than the leg. Tumors on the trunk were more likely than tumors at other sites to be associated with histological evidence of a preexisting nevus. Results of this work indicate that associations between melanoma phenotypic factors may differ by anatomic site.
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PMID:Cutaneous melanoma in women: anatomic distribution in relation to sun exposure and phenotype. 863 53

The atypical mole syndrome (AMS) phenotype, characterised by a large number of common naevi as well as atypical naevi, has been described in families with a genetic susceptibility to melanoma. However, the importance of this phenotype for melanoma in the general population has not been conclusively determined. This study was designed to examine the types and distribution of naevi as well as the prevalence of the AMS phenotype in melanoma patients in England compared with controls. A total of 426 cutaneous melanoma cases (61% of all incident cases) aged 16-75 years were recruited between 1989 and 1993 from the north-east Thames region of the UK and 416 controls from the same age group were recruited over the same period and from the same region. Each subject answered a questionnaire covering demographic details, sun exposure history and other risk factors and underwent a skin examination with total body naevus count performed by a dermatologist. The AMS phenotype was defined using a scoring system. Atypical naevi gave the highest relative risk for cutaneous melanoma, with an odds ratio (OR) of 28.7 (P < 0.0001) for four or more atypical naevi compared with none. Many common naevi were also an important risk factor: the OR for 100 or more naevi 2 mm or above in diameter compared with 0-4 naevi was 7.7 (P < 0.0001). Melanoma was also associated with naevi on sun-exposed sites but also with naevi on non-sun-exposed sites such as the dorsum of the feet, buttocks and anterior scalp. Sixteen per cent of the cases had the AMS phenotype compared with 2% of the controls (OR 10.4, P < 0.0001). The AMS phenotype was more common in males than females (P = 0.008). The odds ratio for the presence of the AMS phenotype was dependent on age, with an odds ratio of 16.1 (95% CI 4.6-57.5) for the presence of the AMS phenotype if aged less than 40 compared with an odds ratio of 6.9 (95% CI 2.9-16.6) if aged 40 or more. The AMS phenotype was strongly predictive of an increased risk of melanoma outside the familial context.
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PMID:Risk of cutaneous melanoma in relation to the numbers, types and sites of naevi: a case-control study. 866 38

Two hundred and thirty-five Korean young men were examined for the count of melanocytic nevi (MN). The mean count of common MN of at least 2 mm diameter was 16.1. Three subjects had more than 50 common MN and another four had clinically atypical MN. We determined skin phototype by interview with questionnaires in the same persons as proposed by Fitzpatrick. All subjects were classified with respect to skin phototype and the number of previous sunburns. The correlations between common MN and the skin phototype or the number of previous sunburns were statistically analyzed. The skin phototype showed the correlation with the number of common MN, which means if skin phototype of any subject belongs to type I, he could to be predicted to have many more common MN than subjects with darker phototypes, like type VI. The correlation between number of previous sunburns and number of common MN was not statistically significant. This study shows persons at moderate risk of cutaneous melanoma (CM) do exist and skin phototype is associated with the prevalence of common MN in Koreans.
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PMID:Counts of common and atypical melanocytic nevi in Korean young men: assessment of their risks and correlations with associated factors. 867 20

Loss of heterozygosity of chromosome region 9p21 occurs commonly and early in sporadic melanoma, suggesting the involvement of a tumor suppressor gene at this locus in the pathogenesis of this neoplasm. Although germline mutations and deletions of the p16INK4 gene located at 9p21 have been reported in familial melanoma, the relative contributions of mutation and deletion in sporadic melanoma are at present unclear. In this study, we investigated 26 cases of sporadic cutaneous melanoma (14 of which demonstrated loss of heterozygosity at 9p21) for mutations of p16INK4. One tumor with allelic loss of 9p contained a CC-->TT mutation at codons 57/58, altering an arginine to a stop codon, consistent with bi-allelic inactivation of p16INK4 in this case. No mutations were identified in any of the other melanomas, or in one benign intradermal nevus with atypical features and two Spitz nevi that also showed loss of heterozygosity of 9p. The inactivation of both copies of p16INK4 in the one case of melanoma adds support to the theory that p16INK4 is important in the development of sporadic cutaneous melanoma, although allelic loss or other methods of inactivation of p16INK4 rather than point mutation appears to be numerically more important. The low frequency of mutation of p16INK4 in cases of sporadic melanoma with loss of heterozygosity of 9p is, however, also consistent with there being another tumor suppressor gene near this locus that is involved in some cases of sporadic melanoma.
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PMID:Infrequent mutation of p16INK4 in sporadic melanoma. 918 29


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