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)

We have previously shown that human metallopanstimulin (MPS-1) is a ubiquitous 9.4-kDa multifunctional ribosomal S27/nuclear "zinc finger" protein which is expressed at high levels in a wide variety of cultured proliferating cells and tumor tissues, including melanoma. In the present study, we have examined the expression of the MPS-1 protein in various types of human benign and malignant melanocytic lesions of the skin. The expression of the MPS-1 protein was studied by immunohistochemistry using specific anti-MPS-1 antibodies. We found that in benign nevi, the staining is weak and in a gradient; most often, only type A melanocytes stain positive. The B and particularly the C types are negative. Remarkably, congenital nevi show a similar gradient staining of regular benign nevi, but in addition one example showed intensely positive dermal nodules adjacent to areas of negative melanocytes. In melanomas, the staining patterns for MPS-1 are more complex. While some melanomas stain evenly and intensely positive, others have remarkably variable expression of MPS-1. The scattered melanocytes migrating to the upper layers of the epidermis are usually intensely positive. In summary, benign lesions stain in an orderly pattern with staining gradients that correlate with the cellular differentiation of the nevi. Malignant melanomas have an erratic, often intense staining that also correlates with the disorderly growth of these neoplasms. These differential results indicate that the MPS-1 antigen is a useful marker for melanocytic lesions at the immunohistochemical level.
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PMID:Differential expression of metallopanstimulin/S27 ribosomal protein in melanocytic lesions of the skin. 940 50

Halo reactions to melanocytic nevi are a well-recognized phenomenon. In contrast, halo reactions to Spitz's nevi have been reported only infrequently. Halo reactions may cause misdiagnosis of an otherwise benign nevus as melanoma because inflammatory cells sometimes obscure the architectural features of the underlying nevus, and may induce cytologic atypia. For Spitz's nevus where the distinction between malignancy and benignancy is already challenging, halo reactions compound the problem. We describe 17 examples of Spitz's nevus with halo reaction, and compare their immunohistochemical features with those of "ordinary" halo nevi. Only 2 of 17 lesions demonstrated clinically apparent halos. Clinical follow-up was available for 12 of 17 cases. None of the 12 has persisted at the biopsy site or metastasized after an average 3.6-year follow-up period. Junctional, compound, intradermal, and combined types of Spitz's nevi were represented. All were characterized by symmetrical lymphocytic infiltrates which permeated the full thickness of the nevus, including junctional nests. Combined Spitz's nevi constituted more than one-half of examples in this series (9/17 cases). The combined Spitz's nevus included a combination of Spitz's nevus with either an ordinary (common, banal) nevus or a superficial congenital type nevus. In these combined Spitz's nevi, the lymphocytic response was often directed exclusively to the Spitz's nevic component. Important distinguishing features from malignant melanoma arising in a pre-existing nevus included symmetry and lateral circumscription of the spitzoid component, no large expansile-appearing aggregates of melanocytes, a decrease in size of nests with increasing dermal depth, a lack of mitotic figures among melanocytes at the base, and a symmetrical and diffusely permeative lymphocytic response. Although the combined Spitz's nevus with halo reaction sometimes appeared asymmetrical at scanning magnification, each component of the combination was symmetrical, when examined independently. Probably because of reactive atypia, nuclear maturation with progressive descent into the dermis was sometimes absent. There were no obvious differences in immunohistochemical staining patterns among 4 Spitz's nevi with halo reaction, 5 regressing melanomas, and 5 benign halo nevi when stained with antibodies to S100, HMB-45, OPD4, CD8, TIA-1, CD1a, CD68, and Ki-67.
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PMID:Spitz's nevi with halo reaction: a histopathologic study of 17 cases. 944 88

Mast cell participation in immune responses, tumor progression, and vascularization has been studied extensively in vitro. In situ investigation of mast cells in routinely processed tissues is hampered by difficulty in reliable detection of mast cells. We studied the tissue density of mast cells using a morphometric point-counting technique in 1 microm-thick, Giemsa-stained, tissue sections from epon-embedded samples of skin biopsies. This technique has been demonstrated to be an accurate and reproducible method for determining mast cell density. Mast cell density in 15 cases of invasive melanoma was compared to that of 9 cases of benign melanocytic nevi and 4 cases of melanoma in situ. Mast cell density was greatest in invasive melanoma (mean density = 0.61 vol.%). The mean density of mast cells in nevi and in situ melanoma was 0.33 and 0.5 respectively. Six of 15 cases of melanoma had mast cell densities > 0.6, whereas mast cell density did not exceed 0.6 in any cases of melanoma in situ or benign melanocytic nevi (p < 0.02). Our findings confirm an increase in mast cell tissue density in some cases of invasive melanoma when compared to mast cell density in benign nevi and in situ melanoma.
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PMID:Increased mast cell density in invasive melanoma. 950 38

In the present study we analyzed, by immunohistochemistry, a panel of human melanomas for protein expression of the cyclin-dependent kinase (cdk) inhibitor p27Kip1 and evaluated whether deregulated expression correlates with clinical outcome for this type of cancer. We found that p27Kip1 was strongly expressed by normal melanocytes and benign nevi, whereas in malignant melanoma, a heterogeneous expression pattern was observed. In the case of nodular melanomas, the level of p27Kip1 was found to correlate significantly with the thickness of the tumor, with less protein expressed in thicker lesions. We also found that patients having tumors with fewer than 5% p27Kip1-staining cells had a significantly higher risk of early relapse of their disease compared with those expressing moderate or high levels. In contrast, the level of p27Kip1 did not correlate with tumor thickness or disease-free survival in patients with superficial spreading melanomas, suggesting that p27Kip1 may play different roles in these two major pathological subgroups of malignant melanoma. Furthermore, p27Kip1 did not appear to have an influence on overall survival for either subgroup. When we examined the combined effect of p21WAF1/CIP1 (another cdk inhibitor) and p27Kip1 on clinical outcome, we found that analysis of these two cdk inhibitors together may have greater prognostic potential than either alone. In conclusion, our results suggest that virtually complete loss of p27Kip1 protein expression has potential importance as a prognostic indicator of early relapse in patients with nodular melanoma The results, furthermore, underscore the value of analyzing multiple cell cycle regulatory proteins to obtain the most reliable indication of prognosis.
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PMID:Protein expression of the cell-cycle inhibitor p27Kip1 in malignant melanoma: inverse correlation with disease-free survival. 966 92

Recent evidence has implicated cyclins and cyclin-dependent kinases in the evolution and progression of various malignancies. We studied the immunohistochemical expression of cyclin A, cyclin B, and cyclin-dependent kinase p34cdc2 in a broad spectrum of benign and malignant melanocytic lesions. Formalin-embedded, parrafin-fixed tissue sections from 66 malignant melanomas (MM) and 60 benign nevi were examined for the expression of these cell-cycle proteins. The results were compared with the standard proliferative marker Ki-67 and mitotic index. MM showed significantly higher immunoreactivity for cyclin A, cyclin B, p34cdc2, and Ki-67 compared with benign nevi. Cyclin A, p34cdc2, and Ki-67 displayed strong co-expression in MM. Overexpression of cyclin A and p34cdc2 correlated with histological type, mitotic activity, Ki-67 index, tumor thickness, Clark's level, and clinical outcome in MM. In invasive MM, increased immunostaining of cyclin A and Ki-67 were associated with decreased patient survival. These findings indicate potential roles of mitotic cyclins and cyclin-dependent kinases in the pathogenesis and progression of malignant melanoma.
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PMID:Mitotic cyclins and cyclin-dependent kinases in melanocytic lesions. 978 46

The first case concerns a 14-year-old girl with a brown conjunctival mass temporally in her right eye which was excised and diagnosed as active conjunctival melanotic lesion. Five years later, a malignant melanoma of the right lacrimal sac and orbit led to general metastatic spread. The second case demonstrates a conjunctival brown mass temporally in the left eye of a 3-year-old boy which enlarged over 4 years. The excision revealed a melanotic lesion which was of uncertain histological dignity. The third case occurred in a 4-year-old boy with a conjunctival glassy tumor temporally in his right eye which after excision led to controversial discussions concerning benign nevus or malignant melanoma.
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PMID:Conjunctival malignant melanoma in children. 988 90

Aggregates of benign nevus cells occurring in lymph nodes are a well-described incidental finding. Nevus cell aggregates (NCAs) can mimic foci of metastatic carcinoma or other disease processes, so the surgical pathologist should be familiar with this lesion. The purpose of this report is to describe the potential diagnostic difficulties created by benign NCAs within the thymus of a 32-year-old man with dysplastic nevus syndrome and malignant melanoma involving mediastinal lymph nodes and the right lung. Morphologically, the NCAs in this case elicited the differential diagnoses of metastatic melanoma and thymoma. Immunohistochemical studies helped to establish the correct diagnosis by demonstrating reactivity for S-100 protein and negative staining for keratin and HMB-45. Unlike malignant melanomas, NCAs show no p53 protein immunoreactivity, and low proliferative activity was detected by Ki-67 antigen immunostaining. Although melanocytic cells were rarely reported in thymic neoplasms, we are not aware of any previous reports of NCAs occurring in the normal thymus.
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PMID:Benign nevus cell aggregates in the thymus: a case report. 1010 20

Angiogenesis is essential for tumor progression and metastasis, however, the angiogenesis regulators that are biologically relevant for human melanoma are still unknown. In this study, we analyzed the expression of the potent angiogenic factor angiogenin (ANG) in human melanoma in vitro and in vivo. Four different human melanoma cell lines and two normal melanocytes were kept either under normoxic or hypoxic conditions. After 24 h of hypoxic culture conditions, ANG was up-regulated in the melanoma cell lines but not in normal melanocytes. Induction levels correlated with the metastatic potential of the cell lines. These data were confirmed by Northern blot analysis. In contrast, induction of vascular endothelial growth factor by hypoxia was equally strong in the examined highly aggressive melanoma cell lines and in one nonaggressive cell line. Other angiogenic factors tested as well as the melanoma growth stimulatory activity (Gro-alpha) showed no up-regulation. Thus, in the present study, hypoxia-induced up-regulation in melanoma cells was only observed for ANG and vascular endothelial growth factor. Immunohistochemical studies showed that 8 of 10 melanomas and all 15 metastases were positive for ANG, particularly in the vicinity of small vessels, whereas all benign nevi were negative. Reverse transcription-PCR detected only weak ANG mRNA in nevi but strong signals in primary melanomas and metastases. In conclusion, we demonstrate for the first time enhanced expression of ANG in highly metastatic cell lines as well as in melanomas and metastases in vivo, suggesting that ANG expression is associated with the metastatic potential.
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PMID:Hypoxia-induced up-regulation of angiogenin in human malignant melanoma. 1019 32

The etiology of malignant melanoma has been intensely studied over the last decade. Much of the recent work focuses on oncongenes and tumour suppressor genes and the role of apoptosis in melanoma. Loss of tumour suppressor proteins such as p16 has been documented in melanoma and correlates with tumour progression. Mutations in the tumour suppressor p53 have also been documented in melanoma. The proto-oncongene Bcl-2 encodes a protein that inhibits apoptosis. Bcl-2 is found in normal melanocytes and benign nevi. However, lower levels are seen in melanoma. To investigate the relationship between melanoma and nevi, in our Basic and Clinical Science section, Dr. Radhi examines the expression of p53, p16, and Bcl in malignant melanoma arriving in benign nevi. P53 immunoreactivity was found only in the malignant component, with no expression being seen in the benign components of the lesion. This suggests that this tumour suppressor gene is involved in the pathogenesis of melanoma.
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PMID:The etiology of malignant melanoma. 1057 55

Tumor-infiltrating lymphocytes (TIL) have been shown to be an independent prognostic factor in melanomas. To better characterize the host immune response, we have classified TIL by their immunoreactivity against lymphoid markers in formalin-fixed, paraffin-embedded tissue. Monoclonal antibodies to leukocyte common antigen (LCA) and TIA-1 (a granule-associated protein of cytotoxic T cells and NK cells) were used to immunostain a series of benign nevi, nontumorigenic radial growth phase, and tumorigenic vertical growth phase melanomas and metastases. Among nine nevi, few LCA+ TIL were found, among which rare cells were positive for TIA-1 (mean, 2.0). Five nontumorigenic radial growth phase melanomas also had few total TIL and rare TIA-1+ TIL (mean, 3.4); the nontumorigenic radial growth phase component of seven tumorigenic vertical growth phase melanomas had higher numbers of TIA-1+ TIL (mean, 11). Twelve cases of tumorigenic vertical growth phase melanoma showed a variable but significantly greater number of both LCA+ TIL and TIA-1+ TIL (mean, 30.6). Nine cases of metastatic melanoma had a wide range of variation in LCA as well as in TIA-1+ TIL (mean, 46). Although the mean total number of TIA-1+ TIL increased from nontumorigenic radial growth phase to tumorigenic vertical growth phase to metastases, TIA-1+ as a percentage of TIL declined across these categories of tumor progression (42%, 31%, and 26%, respectively). Our results show that these attributes of TIA-1+ TIL, both increasing total number but decreasing percentage, appear to be a marker of tumor progression of malignant melanomas. In addition, there was significant variability in the number of TIA-1+ TIL among advanced melanomas, raising the possibility that an assessment of TIA-1+ TIL may prove a useful prognostic tool for the evaluation of primary melanomas.
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PMID:TIA-1 positive tumor-infiltrating lymphocytes in nevi and melanomas. 1065 10


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