UMLS:C0025202 - FACTA Search

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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 hypothesized that lesions that have been termed lentigo maligna can be divided into 2 categories: 1 represents a pigmented lesion that is a precursor to melanoma, and the other melanoma in situ. We and others have hypothesized that there is a progressive acquisition of attributes in pigmented lesions that results in malignant melanoma. Based on these 2 hypotheses, we have predicted that the intraepidermal component of invasive malignant melanomas, lentigo maligna type, should be similar to those lesions that we have termed malignant melanoma in situ, lentigo maligna type rather than lentigo maligna. The intraepidermal component of 42 consecutive cases of invasive malignant melanoma, lentigo maligna type was evaluated by all of the authors. Malignant melanoma in situ, lentigo maligna type is characterized by pagetoid spread, confluence, and nesting of atypical melanocytes. All of the cases evaluated showed features diagnostic of malignant melanoma in situ, lentigo maligna type, in the epidermis overlying the invasive dermal component. We conclude that invasive lentigo maligna melanoma arises in association with those lesions that we have termed malignant melanoma in situ, lentigo maligna type, which may represent a step in the progression between atypical melanocytic hyperplasia (lentigo maligna) and invasive melanoma. This finding supports the distinction of these entities and may have therapeutic implications.
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PMID:Progression to invasive melanoma from malignant melanoma in situ, lentigo maligna type. 1087 64

Matrix metalloproteinases (MMPs) and their specific tissue inhibitors (TIMPs) play an important role in cancer cell invasion and metastasis. Recently, it was shown that the presence of activated MMP-2 correlates with melanoma progression in vitro. This activation involves coordinated expression of MMP-2, membrane-type 1 MMP (MT1-MMP), and TIMP-2. To investigate the expression profile of these enzymes in human melanoma, this study used tumour specimens obtained from both a human melanoma xenograft model, consisting of eight melanoma cell lines with different metastatic capacity in nude mice, and 60 fresh human cutaneous melanocytic lesions comprising all stages of melanocytic tumour progression. MT1-MMP and TIMP-2 mRNA and protein were present in all cell lines. Cell surface expression level of MT1-MMP, as determined by flow cytometry, was similar on all cell lines. In addition, western blot analysis revealed that both inactive and active MT1-MMP protein was expressed by all cell lines. MMP-2 mRNA and the pro-enzyme form of MMP-2 were expressed by all cell lines. Remarkably, the presence of functionally active MMP-2 was restricted to the most aggressive cell lines MV3 and BLM. Reverse transcription-polymerase chain reaction (RT-PCR) analysis of RNA isolated from subcutaneous xenografts revealed MT1-MMP and TIMP-2 mRNA expression in all lesions, whereas MMP-2 mRNA could be detected only in xenografts derived from the highly metastatic cell lines 1F6m, MV3, and BLM. Furthermore, immunohistochemistry demonstrated a marked increase of MMP-2 and MT1-MMP in MV3 and BLM xenografts, whereas TIMP-2 expression showed no evident correlation with metastatic capacity. In human cutaneous melanocytic lesions, MMP-2, MT1-MMP, and TIMP-2 mRNA were detectable by RT-PCR in all lesions. Expression of MMP-2 protein was not detectable, either in common and atypical naevi, or in melanoma in situ by immunohistochemistry. In these lesions, heterogeneous expression of MT1-MMP and TIMP-2 was present in melanocytic cells. In contrast, a large number of MMP-2 and MT1-MMP-positive tumour cells were observed in primary melanomas and melanoma metastases. Double staining experiments and immunohistochemistry on serial sections from the same lesions demonstrated that all tumour cells expressing MMP-2 also expressed MT1-MMP and TIMP-2. Finally, zymography of melanoma metastases revealed that MMP-2 was present in its functionally active form. This study demonstrates that expression of MT1-MMP and TIMP-2 and activation of MMP-2 are correlated with tumour progression both in the xenograft model and in human melanocytic lesions, strongly suggesting that these factors are required for melanoma invasion and metastasis formation.
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PMID:Expression and activation of matrix metalloproteinase-2 (MMP-2) and its co-localization with membrane-type 1 matrix metalloproteinase (MT1-MMP) correlate with melanoma progression. 1087 45

We present the case of a 64-year-old woman who underwent a transhiatal esophagectomy subsequent to the presence of high-grade dysplasia of the esophageal squamous epithelium in repeated biopsies. In the resection specimen chronic esophagitis and multifocal carcinoma in situ of the squamous epithelium were diagnosed, associated with a diffuse intraepithelial proliferation of melanocytic cells. While melanocytic hyperplasia (melanocytosis) has previously been recognized as an occasional reactive lesion that can accompany esophageal inflammation and invasive squamous carcinoma, the present case was unusual because of its cytonuclear and architectural atypia in the melanocytic cell population, resembling features of a melanoma in situ in the absence of manifest invasive malignant melanoma. The disappearance of the melanocytic lesion during follow-up supports its nonneoplastic nature, however. This case illustrates that 'malignant features' in esophageal melanocytosis should be interpreted with caution.
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PMID:Atypical melanocytic proliferation associated with squamous cell carcinoma in situ of the esophagus. 1099 84

Tumor cell invasion and metastasis formation depend on both adhesive and proteolytic mechanisms. Previous studies have shown that expression of matrix metalloproteinase-2 and integrin alphavbeta3 correlate with melanoma progression. Recently, direct binding of matrix metalloproteinase-2 to alpha(v)beta3 was implicated in presenting activated matrix metalloproteinase-2 on the cell surface of invasive cells. In this study we investigated this, using the highly metastatic, alpha(v)beta3-negative melanoma cell lines MV3 and BLM, their beta3-transfected alpha(v)beta3 expressing counterparts, xenografts derived from these cell lines, and fresh human cutaneous melanoma lesions comprising all stages of melanoma progression. Expression and activation status of matrix metalloproteinase-2 were studied by reverse transcription-polymerase chain reaction, immunohistochemistry, western blotting, and zymographic analysis, respectively. Matrix metalloproteinase-2 protein expression in vitro was similar in both alpha(v)beta3-negative and alpha(v)beta3-positive cell lines Remarkable differences, however, exist in the localization of inactive and active matrix metalloproteinase-2. Soluble active matrix metalloproteinase-2 was detectable only in the conditioned medium of alpha(v)beta3-negative cell lines and undetectable in the alpha(v)beta3-positive cell lines. Conversely, active matrix metalloproteinase-2 was present exclusively on the cell surface of the alpha(v)beta3 expressing transfectants. Western blot analysis of other components that are involved in matrix metalloproteinase-2 activation showed that processing of proMT1-matrix metalloproteinase to the activated form was enhanced in beta3 transfectants, whereas secretion of tissue inhibitor of metalloproteinase-2 was decreased. In vivo, the presence of functionally active matrix metalloproteinase-2 was significantly higher in xenografts derived from the alpha(v)beta3 expressing MV3 and BLM cell lines. In human cutaneous melanoma lesions, neither matrix metalloproteinase-2 nor integrin alpha(v)beta3 is detectable in melanoma in situ as determined by immunohistochemistry. In contrast, the number of matrix metalloproteinase-2-positive and alphavbeta3-positive tumor cells was clearly increased in primary melanomas, and melanoma metastases. Double staining experiments and confocal laser microscopy demonstrated that the percentage of cells coexpressing matrix metalloproteinase-2 and alpha(v)beta3 increased in advanced primary melanomas and melanoma metastases. In addition, zymography showed that functionally active matrix metalloproteinase-2 was frequently present in melanoma metastases. In these lesions a high proportion of matrix metalloproteinase-2- and alphavbeta3-double-positive melanoma cells were detectable. Our study demonstrates that the presence of activated matrix metalloproteinase-2 correlates with expression of alpha(v)beta3 in human melanoma cells both in vitro and in vivo, and also in fresh human melanoma lesions. These findings strongly suggest that co-ordinated expression of both factors may be required for melanoma cell invasion and metastasis formation.
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PMID:Coexpression of integrin alpha(v)beta3 and matrix metalloproteinase-2 (MMP-2) coincides with MMP-2 activation: correlation with melanoma progression. 1099 34

The stages defining the progression pathway of human melanoma are atypical nevi, the precursor lesions and risk markers of melanoma, melanoma in situ and melanoma in the radical growth phase (RGP), which represent the early stages of melanoma development, and primary melanoma in the vertical growth phase (VGP) and melanoma in the metastatic growth phase (MGP), which are the advanced stages of the disease. Unlike cells obtained from VGP and MGP melanomas, which can be established as cell lines, cells derived from atypical nevi, melanoma in situ, and RGP melanoma cannot be propagated in vitro. Thus, information regarding molecular markers that may be differentially expressed in the early versus the advanced stages of this disease can only be obtained from the analysis of specimens. Since activation of telomerase and deregulation of apoptosis contribute to the pathogenesis of a significant number of human malignancies, we conducted a study, using nevus and melanoma specimens, to determine at what stage in the progression pathway of melanoma, telomerase activity can first be detected, and whether concordant with telomerase activation, one might observe a stage-specific switch from expression of promoters to inhibitors of apoptosis. The findings described here, demonstrate telomerase activity in some but not all MGP melanomas and not in any of the preceding pathological stages, and no apparent imbalance between pro- and anti-apoptotic markers in telomerase-positive MGP melanomas compared to telomerase-negative nevi and telomerase-negative VGP and MGP melanomas.
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PMID:Telomerase activity and expression of apoptosis and anti-apoptosis regulators in the progression pathway of human melanoma. 1102 92

Acral melanoma may present clinically and histologically with atypical features causing a delay in proper diagnosis. The aim of the present study was to assess the frequency of a histological variant with clear cell changes. Clinical information, hematoxylin & eosin stained paraffin sections and immunohistochemical staining profiles were reviewed in 49 cases of acral melanoma. Twenty-one (43%) specimens contained tumor cells with clear cell changes in focal areas, whereas in 7 (14%) specimens clear cells were the major tumor constituting cells. The tumor thickness ranged from melanoma in situ to 14 mm. Immunohistochemistry demonstrated weak staining for S100 and HMB45 as well as strong positivity for Melan A and NK1C3. Recognition of clear cell features is important since differential diagnosis includes a variety of other clear cell malignancies, among them metastasis from renal cell carcinoma, clear cell sarcoma and hidradenocarcinoma.
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PMID:Clear cells in acral melanoma. 1117 32

Several reports have documented the coexistence of basal cell carcinoma (BCC) with other lesions, including melanoma. This study was performed to determine whether nests of BCC contain benign melanocytes and Langerhans [corrected] cells. Ten cases of BCC were investigated to determine whether benign melanocytes and Langerhans [corrected] cells populate tumor nests. The BCCs were stained with antibodies to cytokeratin AEI/AE3, S-100, HMB-45, Melan-A, and CD1a proteins. We report that all 10 BCCs were populated by dendritic melanocytes distributed at the periphery (5/10 cases) or evenly throughout tumor nests (5/10 cases). Clusters of melanocytes were not identified in any of the BCCs. A total of 9 of 10 tumors showed staining of dendritic Langerhans cells with CD1a. A total of 8 of 10 tumors stained with cytokeratin AEI/AE3; in 6 of the 8 tumors, the staining was focal. We compared these findings with a single example of a BCC and melanoma in situ (MIS) collision tumor in which the cytokeratin AE1/AE3-positive epithelial nests of BCC were populated by a high density of malignant melanocytes that stained with S-100 and HMB-45. Melanocytes were disposed singly and in clusters of two or more cells within BCC tumor nests. We conclude from this study that BCCs are regularly populated by benign melanocytes and Langerhans [corrected] cells. Furthermore, when BCC is infiltrated with malignant melanocytes of MIS, the melanocyte density is higher and clusters of melanocytes can be observed. The significance of these two findings is unclear, as additional cases of BCC MIS collision tumor need to be studied.
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PMID:Basal cell carcinomas are populated by melanocytes and Langerhans [correction of Langerhan's] cells. 1180 3

Cancers of various sorts are occasionally encountered in burn scars. These lesions are usually squamous cell carcinomas, and the burn scars are usually old. Very rarely, malignant melanoma is encountered. An 87-year-old nursing home patient who had been burned by a lightening strike at age 16 was evaluated. She had sustained a wound covering 2% or 3% of her body surface involving her neck and the upper portion of her anterior trunk that had required several grafts. A lesion was noted over the suprasternal notch approximately 3 months before admission. The biopsy was reported as malignant melanoma. She was subsequently treated by wide reexcision with an associated Z-plasty for neck release. Because of the patient's age and the presence of four areas of regional lymph nodes nearby into which metastasis might spread, no lymph node dissections were carried out. The specimen from the reexcision was reported as squamous cell carcinoma in situ, melanoma in situ, and multinucleated giant cell reaction, acute and chronic infiltrates. The wound margins were clear.
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PMID:Malignant melanoma in a burn scar. 1119 38

A case of gallbladder involvement by malignant melanoma in a 57-year-old woman is reported. The gallbladder, resected for cholelithiasis, harboured a pedunculated polypoid dark mass, which histologically revealed sheets and nests of epithelioid cells with hyperchromatic nuclei in the lamina propria and at the junctional level. These cells were pigmented (with positive reaction with Schmorl's stain and bleaching with peroxide) and showed immunohistochemical positivity for S-100, gp 100 antigen (HMB-45 antibody) and vimentin. The patient, affected by dysplastic naevus syndrome, had a melanoma in situ excised from the scalp 8 years earlier. The features of the investigated lesion address towards a diagnosis of primary gallbladder melanoma. Furthermore, this is the first time that the existence of such a controversial entity is sustained by the ultrastructural investigation of melanosomes, demonstrating the presence of two melanocitary populations, a typical one exclusively junctional and an atypical one both at the junctional level and in the lamina propria.
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PMID:Primary malignant melanoma of the gallbladder in dysplastic naevus syndrome. 1125 18

Recent advancement in the research of malignant melanoma is reviewed. Among many gene alterations detected in human melanoma, defect of CDKN2A located at chromosome 9p21 seems to be most important in the earlier developmental phase, though significance of this gene in the evolution of melanoma in situ has not been confirmed yet. Deletions of PTEN/MMAC1 on 10q23.3 and AIM1 on 6q21 as well as mutations of ras gene are involved in the later progression stages of melanoma. Adhesion molecules relevant to development and progression of melanoma have been intensely investigated in recent years, revealing crucial roles of cadherins and alpha(v)beta(3) integrin in the biologic behaviors of melanoma cells. Melanoma is characterized by extremely high potential of developing metastases. Dynamic changes of matrix metalloproteinase activity during invasion and movement of melanoma cells may be a major concern in this field. Fragility of blood vessels in melanoma lesions is another important point related to hematogeneous metastases. Acral lentiginous melanoma is a unique subtype of melanoma, because, in contrast to other subtypes, ultraviolet irradiation is not a major factor in its development. Investigation of pathogenesis of acral lentiginous melanoma surely provides us with new information about mechanism of melanocyte transformation. Recent advances in the management of malignant melanoma are also briefly reviewed, such as biochemotherapy, immunotherapy, and gene therapy. Finally, the concept of molecular classification of melanoma by gene expression profile is introduced, which possibly enables us to give the tailor-made therapy for each melanoma patient in the near future.
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PMID:Recent advances in melanoma research. 1132 15

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