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

Melanoma often develops from clinically and histologically well-defined precursor lesions. During progression of normal melanocytes to benign nevi, dramatic changes in the expression of adhesion receptors are observed, most notably loss of E-cadherin which mediates adhesion of melanocytes to keratinocytes, and gain of Mel-CAM which predominantly mediates heterotypic adhesion between cells. Major changes in adhesion receptors also occur when cells progress from dysplastic nevi or biologically early radial-growth-phase primary melanomas to biologically late (tumorigenic) vertical-growth-phase primary melanomas. The integrin subunit beta 3 is up-regulated, whereas other integrins such as alpha 6 beta 1 and alpha V beta 1 are down-regulated. This review highlights the major changes in adhesion receptor expression on melanocytes at various stages of tumor progression.
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PMID:Adhesion receptors in human melanoma progression. 765 8

We evaluated three cases of pigmented pulmonary carcinoid tumors that were retrieved from the files of the Armed Forces Institute of Pathology, Washington, DC. Clinical follow-up showed no indication of tumor recurrence or metastases, nor was there evidence of malignant melanoma. All three cases exhibited histologic features of typical carcinoid tumor; there were focal oncocytic changes in two cases. Finely dispersed, brown pigment, believed to be melanin, was distributed in two different patterns: in sustentacular cells (case 1) or within the tumor cells (cases 2 and 3). Fontana-Masson stain was positive in areas of this pigment in all cases. The tumor cells showed immunoreactivity for chromogranin, synaptophysin, keratin (AE1/AE3 and CAM-5.2), and S100 protein in all cases. Focal staining for vimentin and corticotropin was seen within neoplastic cells in two cases. The pigmented sustentacular cells in case 1 showed focal immunoreactivity for S100 protein and HMB-45. Ultrastructural studies of paraffin-embedded tissues were performed in two cases. They showed well-developed melanosomes in the pigmented sustentacular cells in case 1. In both cases, cytoplasmic neurosecretory-type granules were identified in neoplastic cells. These findings demonstrate that pigmented pulmonary carcinoid tumor has an immunohistochemical profile similar to that of typical pulmonary carcinoid tumor. In some instances, pigmented pulmonary carcinoid tumors may show ultrastructural evidence of melanocytic and neuroendocrine differentiation. These immunohistologic and ultrastructural findings distinguish pigmented pulmonary carcinoid tumor from malignant melanoma and support the concept of "multidirectional cellular differentiation."
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PMID:Pigmented pulmonary carcinoid tumor. An immunohistochemical and ultrastructural study. 768 14

Four cases of cutaneous epithelioid angiosarcoma are described together with the potential diagnostic trap of mistaking these tumours for poorly differentiated carcinoma or malignant melanoma. The immunophenotypic profile using four endothelial markers showed positive staining in all cases for factor VIII related antigen in a predominantly paranuclear dot-like fashion and for CD31 (JC70); in three cases for CD34 (QB-END/10) and in two cases with UEA-1. All four cases were cytokeratin (CAM 5.2 and AE1/AE3) negative in contrast to the positive staining reported at non-cutaneous sites. Aberrant S-100 protein expression was seen in one case. In two cases subsequent recurrences showed better differentiation than the original tumour. Electronmicroscopy confirmed the absence of non-endothelial lines of differentiation but failed to reveal Weibel-Palade bodies.
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PMID:Cutaneous epithelioid angiosarcoma: a clinicopathological study of four cases. 786 82

The cell-cell adhesion receptor, Mel-CAM/MUC18, is highly expressed on metastatic melanoma cells and is also detectable on primary melanomas but not on normal melanocytes. Previous studies have shown that increased Mel-CAM/MUC18 expression correlates with tumor thickness and metastatic potential. We show here that normal melanocytes and nevus cells in culture express Mel-CAM/MUC18, but expression is down-regulated when cells are co-cultured with keratinocytes. Such keratinocyte-mediated regulation of Mel-CAM/MUC18 expression on melanocytes, nevus cells, and early melanomas can also be demonstrated in situ in patients' specimens. On the other hand, melanoma cells from primary and metastatic lesions constitutively express Mel-CAM/MUC18, and keratinocytes have no modulatory effect. These results suggest that contact between keratinocytes and human melanocytic cells modulates Mel-CAM/MUC18 expression, raising the possibility that escape from keratinocyte control during melanoma development leads to expression of antigens that contribute to the malignant phenotype.
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PMID:Regulation of Mel-CAM/MUC18 expression on melanocytes of different stages of tumor progression by normal keratinocytes. 794 74

An immunohistochemical study of 106 malignant melanoma specimens from 59 patients, using formalin-fixed, paraffin-embedded material, is reported. Negativity for HMB-45 was seen in 11% of specimens. The rate of positivity with CAM 5.2 was 7%. One specimen showed alpha-smooth muscle actin (alpha SMA) positivity. For 11 of the 12 cases in which anomalous immunophenotypes were seen, multiple specimens were available; nine of these showed evidence of an alteration in the immunophenotype between specimens. Comparing the primary tumours with local recurrences and metastases, there was, variously, loss of HMB-45, S-100 protein and NKI/C3 positivity, and acquisition of CAM 5.2 and alpha SMA positivity. In some cases, the change of immunophenotype appeared to occur in a single step. However, one case with six consecutive specimens showed evidence of progressive loss of HMB-45, S-100 protein and NKI/C3 with concomitant gain of CAM 5.2 staining. The implications for the use of immunophenotyping in diagnostic practice are discussed.
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PMID:An immunophenotypic survey of malignant melanomas. 840 88

Integrin alpha v beta 3 is distinct in its capacity to recognize the sequence Arg-Gly-Asp (RGD) in many extra-cellular matrix (ECM) components. Here, we demonstrate that in addition to the recognition of ECM components, alpha v beta 3 can interact with the neural cell adhesion molecule L1-CAM; a member of the immunoglobulin superfamily (IgSF). M21 melanoma cells displayed significant Ca(++)-dependent adhesion and spreading on immunopurified rat L1 (NILE). This adhesion was found to be dependent on the expression of the alpha v-integrin subunit and could be significantly inhibited by an antibody to the alpha v beta 3 heterodimer. M21 cells also displayed some alpha v beta 3-dependent adhesion and spreading on immunopurified human L1. Ligation between this ligand and alpha v beta 3 was also observed to promote significant haptotactic cell migration. To map the site of alpha v beta 3 ligation we used recombinant L1 fragments comprising the entire extracellular domain of human L1. Significant alpha v beta 3-dependent adhesion and spreading was evident on a L1 fragment containing Ig-like domains 4, 5, and 6. Importantly, mutation of an RGD sequence present in the sixth Ig-like domain of L1 abrogated M21 cell adhesion. We conclude that alpha v beta 3-dependent recognition of human L1 is dependent on ligation of this RGD site. Despite high levels of L1 expression the M21 melanoma cells did not display significant adhesion via a homophilic L1-L1 interaction. These data suggest that M21 melanoma cells recognize and adhere to L1 through a mechanism that is primarily heterophilic and integrin dependent. Finally, we present evidence that melanoma cells can shed and deposit L1 in occluding ECM. In this regard, alpha v beta 3 may recognize L1 in a cell-cell or cell-substrate interaction.
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PMID:Human neural cell adhesion molecule L1 and rat homologue NILE are ligands for integrin alpha v beta 3. 863 23

The bcl-2 proto-oncogene, which is involved in the regulation of apoptosis, is expressed in a wide variety of fetal and adult tissues. We and others have demonstrated recently that in the human skin melanocytes, nervus cells and melanoma cells express bcl-2 constitutively. In the present study, we have analysed the expression of bcl-2 in Merkel cells and in Merkel cell carcinomas. In 2 colour immunofluorescence staining, normal human Merkel cells as identified by the expression of cytokeratins 8, 18 and 20, were also anti-bcl-2 positive. Staining of paraffin sections of Merkel cell carcinomas with an anti-bcl-2 monoclonal antibody revealed strong bcl-2 protein immunoreactivity in all 5 tumors tested. Serial sections of Merkel cell carcinomas stained with the monoclonal antibodies CK 20, CAM 5.2, anti-neuron-specific enolase and anti-bcl-2 showed that the anti-bcl-2 reactive cells were indeed tumor cells. Our data demonstrate for the first time, that normal human Merkel cells and Merkel cell carcinomas express bcl-2 constitutively. Considering the biological function of the bcl-2 proto-oncogene, i.e., its anti-apoptotic effect, it is conceivable that in the near future, modulations of the expression of this protein may offer a new strategy in the therapy of bcl-2 expressing tumors such as Merkel cell carcinoma.
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PMID:Merkel cells and Merkel cell carcinoma express the BCL-2 proto-oncogene. 884 Jan 59

The bel-2 proto-oncogene, which is involved in the regulation of apoptosis, is expressed in a wide variety of fetal and adult tissues. We and others have demonstrated recently that in the human skin melanocytes, nevus cells and melanoma cells express bcl-2 constitutively. In the present study, we have analysed the expression of bcl-2 in Merkel cells and in Merkel cell carcinomas. In 2 colour immunofluorescence staining, normal human Merkel cells as identified by the expression of cytokeratins 8, 18 and 20, were also anti-bcl-2 positive. Staining of paraffin sections of Merkel cell carcinomas with an anti-bcl-2 monoclonal antibody revealed strong bcl-2 protein immunoreactivity in all 5 tumors tested. Serial sections of Merkel cell carcinomas stained with the monoclonal antibodies CK 20, CAM 5.2, anti-neuron-specific enolase and anti-bcl-2 showed that the anti-bcl-2 reactive cells were indeed tumor cells. Our data demonstrate for the first time, that normal human Merkel cells and Merkel cel carcinomas express bcl-2 constitutively. Considering the biological function of the bcl-2 proto-oncogene, i.e., its anti-apoptotic effect, it is conceivable that in the near future, modulations of the expression of this protein may offer a new strategy in the therapy of bcl-2 expressing tumors such as Merkel cell carcinoma.
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PMID:Merkel cells and Merkel cell carcinoma express the BCL-2 proto-oncogene. 873 19

A comparative immunohistochemical study was performed on Paget's disease of the nipple (PDN), extramammary Paget's disease (EMPD) and cutaneous superficial spreading melanoma (SSM) using antibodies to S100, NK1-C3 and HMB45, cytokeratin (CAM 5.2) and c-erb B2 oncoprotein (21N). Conventional histochemical stains for intracytoplasmic mucin and melanin were also done. Of the 20 cases of PDN, positivity was seen in 12 with S100, 16 with NK1-C3, none with HMB45, 20 with CAM 5.2 and 19 with 21N. All 5 cases of EMPD were CAM 5.2 positive and HMB45, S100 and 21N negative. Three EMPD were NK1-C3 positive. All 10 cases of SSM were S100, NK1-C3 and HMB45 positive and all were CAM5.2 and 21N negative. Mucin was demonstrable in 11 cases of PDN and all of EMPD but none of SSM. Melanin was seen in 2 PDN, 3 EMPD and all SSM cases. Identification of mucin and melanin, therefore, proved an unreliable means of distinguishing these diseases. Immunohistochemistry for cytokeratin and HMB45 appear to be the most specific markers in differentiating Paget's disease and SSM. Antibodies to c-erb B2 may also be valuable in this situation.
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PMID:A comparative immunohistochemical study of mammary and extramammary Paget's disease and superficial spreading melanoma, with particular emphasis on melanocytic markers. 898 82

The clinical and pathological features of a nonulcerated desmoplastic melanoma in the vulva of a 52-year-old woman are presented. Pleomorphic neoplastic spindle cells, fibroblasts and collagen formed a poorly demarcated 18 mm dermal mass. No adjacent intraepidermal component was seen. Immunoreactivity was demonstrated for S100 protein, vimentin, neuron-specific enolase and actin, but not for HMB-45, CAM 5.2, cytokeratin, epithelial membrane antigen, desmin or CD34. Electron microscopic examination was noncontributory. Treatment included a left hemivulvectomy with ipsilateral groin node dissection followed by radiotherapy. The tumor recurred six weeks later and was unresectable. The patient is alive with symptoms nine months after presentation. This is the first case report of a vulvar desmoplastic melanoma without neural involvement or an intraepidermal component. The variable tumor cytomorphology, nonspecific immunohistochemical and ultrastructural features render a diagnosis more difficult than with other primary cutaneous melanomas.
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PMID:Desmoplastic melanoma of the vulva. 921 52


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