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ABSTRACT: The differential diagnosis between benign Spitz nevus and malignant melanoma may present considerable difficulties in some cases. Here we report 2 unusual melanocytic tumors with spitzoid features developing in acral sites of Japanese patients to illustrate the use of comparative genomic hybridization (CGH) to classify these lesions. Case 1 was a 12-mm-thick, >2 cm-diameter nodule on the sole of a 37-year-old man. Case 2 was a subungual tumor of the left index finger in a 13-year-old boy. CGH showed absence of chromosomal aberrations in case 1 and multiple aberrations in case 2, including focused amplification as previously described in acral melanomas. Case 1 was free of disease after 2.5 years of follow-up, whereas case 2 developed lymph node metastasis. We conclude that molecular techniques such as CGH can be of diagnostic help in the classification of histologically ambiguous lesions.
Human Pathlogy 01/2003; 34(1):89-92. · 2.88 Impact Factor
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ABSTRACT: We investigated whether repeated cationic multilamellar liposome-mediated gene transfers enhanced the transduction efficiency against murine melanoma cell lines and experimental subcutaneous melanoma. In the former, the murine melanoma cell line, B16F10, was transfected by our original cationic multilamellar liposomes containing pVLacZ, which express beta-galactosidase in eukaryotic cells. Cells were exposed to the liposomes in a single, double, or triple procedure during the cell logarithmic proliferative period. We then evaluated the transduction efficiency by X-gal staining and beta-galactosidase assay. The number of positive cells and level of beta-galactosidase activity were significantly increased by repeated exposures compared with a single one. Cells transfected by the fluorescently labeled cationic liposome containing pEGFP-C1 showed both an increased uptake of liposomes and an increased number of EGFP expression cells following repeated exposures. In the latter, murine subcutaneous melanomas, which were made by transplantation of B16F10 in C57BL6 mice, were transfected by same liposomes. Subcutaneous melanomas were exposed to the liposomes in a single, double, or triple procedure. We then evaluated the transduction efficiency by the beta-galactosidase assay. The level of beta-galactosidase activity was significantly increased by repeated exposures compared with a single one. The results indicate that repeated exposures to the liposomes enhanced the transduction efficiency toward murine melanoma cells and experimental subcutaneous melanoma, and may provide a basis for the repeated-exposure protocol for human trials.
Journal of Dermatological Science 10/2002; 29(3):206-13. · 3.72 Impact Factor
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ABSTRACT: Galectin-9 expression was examined in 6 human melanoma cell lines. Among them, MM-BP proliferated with colony formation, but MM-RU failed. RT-PCR analysis revealed evident expression of galectin-9 mRNA in MM-BP but not in MM-RU. MM-BP expressed galectin-9 protein both on the surface and in the cytoplasm, whereas MM-RU expressed it only weakly in the cytoplasm. Exogenous galectin-9 induced in vitro both cell aggregation and apoptosis of MM-RU proliferating without colony formation. Association of galectin-9 expression in melanoma cells with prognosis of the patients bearing melanocytic tumors was further examined. Galectin-9 protein was strongly and homogeneously expressed in melanocytic nevi, but down-regulated in melanoma cells especially in metastatic lesions. High galectin-9 expression was inversely correlated with the progression of this disease, suggesting that high galectin-9 expression in primary melanoma lesions links to a better prognosis.
International Journal of Cancer 07/2002; 99(6):809-16. · 5.44 Impact Factor
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ABSTRACT: Tissue factor (TF) is involved in tumor progression and metastatic potency in some malignant tumors and its function is regulated by tissue factor pathway inhibitor (TFPI) therefore the interaction of both molecules is crucial for their functional role. We evaluated the clinical relevance of TF and TFPI expression in benign and malignant melanocytic lesions. Expression of both was examined by immunoperoxidase staining using serial tissue sections in 16 nevi, 34 primary and 15 metastatic melanoma lesions. TF and TFPI were ubiquitously expressed in benign and malignant melanocytic lesions. This finding was confirmed by Western blot analysis using cultured human melanocytes, nevi cells (NCN) and melanoma cell lines. Although TF expression was not associated with malignant transformation and disease progression, TFPI expression in primary and metastatic melanoma lesions was significantly lower and weaker than that in nevi lesions in terms of intensity and percentage of stained cells. In addition, TFPI expression in metastatic lesions was significantly lower and weaker than that of TF. These results suggest that the relative expression of TF to TFPI may play a crucial role in the malignant transformation and metastatic potency in melanocytic cells.
Pigment Cell Research 07/2002; 15(3):212-6. · 4.29 Impact Factor
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ABSTRACT: Galectin-9 expression was examined in 6 human melanoma cell lines. Among them, MM-BP proliferated with colony formation, but MM-RU failed. RT-PCR analysis revealed evident expression of galectin-9 mRNA in MM-BP but not in MM-RU. MM-BP expressed galectin-9 protein both on the surface and in the cytoplasm, whereas MM-RU expressed it only weakly in the cytoplasm. Exogenous galectin-9 induced in vitro both cell aggregation and apoptosis of MM-RU proliferating without colony formation. Association of galectin-9 expression in melanoma cells with prognosis of the patients bearing melanocytic tumors was further examined. Galectin-9 protein was strongly and homogeneously expressed in melanocytic nevi, but down-regulated in melanoma cells especially in metastatic lesions. High galectin-9 expression was inversely correlated with the progression of this disease, suggesting that high galectin-9 expression in primary melanoma lesions links to a better prognosis. © 2002 Wiley-Liss, Inc.
International Journal of Cancer 04/2002; 99(6):809 - 816. · 5.44 Impact Factor
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ABSTRACT: The αvβ3 integrin has emerged as a key mediator in angiogenesis. Its role in tumor-induced angiogenesis is supported by its up-regulation
in vivo in the vasculature of a number of different types of carcinoma. The potential clinical significance of αvβ3 expression on blood vessels in carcinomas is suggested by its association with tumor progression. Currently no information
is available about the clinical significance of αvβ3 expression on the vasculature of lesions of melanocytic origin. Since we have previously found that αvβ3 expression on melanoma cells in primary lesions is associated with a poor prognosis, in the present study we have compared
αvβ3 expression on blood vessels and on cells of melanocytic origin in nevi and in malignant melanoma lesions. In addition we
have examined the lesions for expression of the αv subunit to gain information on the regulation of αvβ3 expression on endothelial cells and on cells of the melanocyte lineage. αvβ3 expression on endothelial cells and on melanocytic cells was a relatively sensitive and specific marker for malignant lesions.
However, αvβ3 expression on endothelial cells in primary melanoma lesions was not associated with the prognosis of the disease. The αv subunit and the αvβ3 complex were differentially expressed on endothelial cells and on melanocytic cells, implying that different regulatory pathways
control their expression. This finding may account for the differential clinical significance of αvβ3 expression on tumor vasculature and on melanoma cells we observed in our patient cohort. Lastly, αvβ3 may be a useful target for immunotherapeutic approaches in melanoma because of its high expression on the vasculature of
all metastatic lesions tested and its restricted distribution in normal tissues.
Cancer Immunology and Immunotherapy 06/2000; 49(6):314-318. · 3.70 Impact Factor
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ABSTRACT: Despite its potential clinical relevance, αvβ3 expression has been analyzed only in a limited number of melanoma lesions, mostly nodular melanoma (NM) and superficial spreading melanoma (SSM). Therefore, in the present study, we have correlated αvβ3 expression in 33 acral lentiginous melanomas (ALMs), 6 lentigo maligna melanomas, 7 mucosal melanomas, 12 NMs and 9 SSMs with their antigenic profile, with their histo-pathological characteristics and with the clinical course of the disease. Furthermore, we have compared αvβ3 expression in ALM lesions with that in NM and SSM lesions since this information helps to clarify the relationship of the latter 2 histotypes with ALM. Such a relationship is uncertain since ALM has a clinical course similar to that of NM and SSM despite different antigenic profiles and biological characteristics. The level of αvβ3 expression in primary lesions was not correlated with that of high-m.w. melanoma-associated antigen and intercellular adhesion molecule-1, with lesion thickness and with disease recurrence in ALM but was significantly correlated with these 4 parameters in the other melanoma histotypes analyzed. Therefore, αvβ3 expression appears to have a differential clinical significance in ALM and in the other histotypes of melanoma we have analyzed since it appears to play a significant role in the progression of the disease only in non-ALM histotypes. Int. J. Cancer (Pred. Oncol.) 89:153–159, 2000. © 2000 Wiley-Liss, Inc.
International Journal of Cancer 03/2000; 89(2):153 - 159. · 5.44 Impact Factor
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ABSTRACT: In recent years, the mechanisms underlying defects in the expression/function of human leukocyte antigen (HLA) class I antigens have been analyzed in an increasing number of melanoma cells, since these abnormalities are likely to have a negative impact on T-cell-based immunotherapy of melanoma. This article reviews the information about the molecular defects found in melanoma cell lines that do not express HLA class I antigens, following a concise description of the structure and assembly of HLA class I antigens. Distinct defects ranging from large deletions to point mutations in [beta]2-micro-globulin genes have been found in melanoma cells. A mutation in an 8 base-pair CT repeat region of exon 1 has been found frequently in melanoma cell lines suggesting that this region of the [beta]2-microglobulin gene is a hot-spot for mutations. The effects of [beta]2-microglobulin mutations are mostly at the level of translation, emphasizing the importance of analyzing [beta]2-microglobulin expression at the protein level in melanoma lesions without detectable HLA class I antigen expression. Interestingly, many melanoma cell lines have additional defects that directly impact HLA class I antigen expression. Therefore, multiple mechanisms that affect the expression/function of HLA class I antigens appear to be available to melanoma cells to escape from immune recognition.
(C) Lippincott-Raven Publishers.
Melanoma Research 07/1997; 7. · 2.19 Impact Factor
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ABSTRACT: Ten primary and 6 metastatic mucosal melanoma lesions were tested, utilizing the immunoperoxidase reaction with a panel of 26 monoclonal antibodies (MAbs). The latter included MAbs recognizing membrane-bound and cytoplasmic-melanoma-associated antigens, adhesion molecules and their receptors, and HLA Class-I and Class-II antigens. The melanoma lesions displayed differential reactivity with the panel of MAbs. Mucosal melanoma lesions differ from other types of melanoma in their antigenic profile, since they are the only type of melanoma to display a higher expression of p97 MAA, CEA-MAA and NGF-R in primary lesions than in metastatic ones. Furthermore, the pattern of HMW-MAA expression in mucosal melanoma lesions is different from that in nodular and uveal melanoma lesions and only partly resembles that observed in acral lentiginous melanoma lesions. Like other types of melanoma, mucosal melanoma lesions display a heterogeneous expression of HLA antigens, a selective loss of reactivity with some of the anti-HLA Class-I MAbs and a higher frequency of abnormalities in HLA Class-I antigen expression in metastatic than in primary lesions. Expression of HMW-MAA, 110-kDa MAA, p97 MAA, CEA-MAA, NGF-R and GD2 ganglioside in primary melanoma lesions was found to be associated with a poor prognosis. Although preliminary in nature, these results suggest that analysis of mucosal melanoma lesions with MAbs, in conjunction with information about the clinical course of the disease, will contribute to determine the biological and clinical significance of the distinct characteristics of the antigenic profile of mucosal melanoma lesions.
International Journal of Cancer 01/1994; 56(3):370 - 374. · 5.44 Impact Factor
