Molecular Pathology of Malignant Melanoma

Słomiński, Andrzej; Wortsman, Jacobo; Nickoloff, Brian J.; McClatchey, Kenneth D.; Mihm, Martín C.; Ross, Jeffrey S.

doi:10.1093/ajcp/110.6.788

Cited by 26 publications

(23 citation statements)

References 46 publications

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“…[19][20][21][37][38][39] However, the present study is the first to assess clonal genetic relationships between primary melanomas and an uncommon subtype of metastasis, the epidermotropic metastatic melanoma. The importance of studying this relationship is underscored by the fact that histopathology alone may be insufficient to distinguish an epidermotropic metastatic melanoma from a new primary lesion.…”

Section: Discussionmentioning

confidence: 98%

Clonal relationships between epidermotropic metastatic melanomas and their primary lesions: a loss of heterozygosity and X-chromosome inactivation-based analysis

et al. 2007

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Loss of heterozygosity (LOH) has previously been demonstrated at multiple chromosome microsatellites in primary and metastatic melanomas. Epidermotropic metastases of melanoma are unique in their varied histopathologic appearance, which can mimic a primary lesion. Our objective was to compare LOH profiles in primary and epidermotropic metastatic melanoma to delineate their clonal relationship. We examined the pattern of allelic loss in the primary melanomas of nine patients in addition to the 21 corresponding epidermotropic metastatic melanomas (average 2.3 metastases per patient). DNA samples were prepared from formalin-fixed, paraffin-embedded tissue sections using laser capture microdissection. Eight DNA microsatellite markers on six different chromosomes were analyzed: D1S214 (1p), D6S305 (6q), D9S171 (9p), D9S157 (9p), IFNA (9p), D10S212 (10q), D11S258 (11q), D18S70 (18q). In addition, X-chromosome inactivation analysis was performed in tumors from four women. LOH was seen in 67% (6/9) of primary melanomas and 81% (17/21) of epidermotropic metastatic melanomas. The most frequent allelic losses in informative cases occurred at 10q (33%), 9p (22%), and 11q (22%) in primary melanomas, and at 10q (50%), 1p (44%), and 6q (39%) in epidermotropic metastatic melanomas. Primary lesions demonstrating LOH had concordant allelic loss in at least one locus in a corresponding epidermotropic metastatic melanoma in 83% (5/6) of cases. X-chromosome analysis showed nonrandom inactivation in 75% (3/4) and 71% (5/7) of primary melanoma and epidermotropic metastatic melanoma cases, respectively. Our LOH and X-chromosome inactivation analysis data suggest that epidermotropically metastatic melanomas are clonally related to their primary lesion in many cases. Our data also indicated that some cases diagnosed as epidermotropic metastatic melanoma might be divergent clones or new primaries rather than metastatic disease.

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Section: Discussionmentioning

confidence: 98%

Clonal relationships between epidermotropic metastatic melanomas and their primary lesions: a loss of heterozygosity and X-chromosome inactivation-based analysis

et al. 2007

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“…White people all over the world have experienced an increase in incidence, which has doubled in the last decade [1]. Melanoma occurs in young adults and, when metastatic, is poorly responsive to therapy [2][3][4]. An effective cure can be obtained if diagnosis and excision are performed early [5].…”

Section: Introductionmentioning

confidence: 99%

Cell adhesion and communication proteins are differentially expressed in melanoma progression model☆☆☆★

et al. 2011

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“…The long arm of the sixth chromosome (6q) is known to harbour LOH frequently in cutaneous melanoma (Millikin et al, 1991;Walker et al, 1994;Robertson et al, 1996;Slominski et al, 1998) and in other cancers (Foulkes et al, 1993;Noviello et al, 1996). So far, chromosomal losses confined specifically to the short arm of the chromosome 6 (6p) near the location of TFAP2A in 6p24 have been documented in melanoma cell lines (Real et al, 1998;Turner et al, 1998) and in several other malignancies (Foulkes et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

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et al. 2000

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SummaryThe loss of transcription factor AP-2α expression has been shown to associate with tumourigenicity of melanoma cell lines and poor prognosis in primary cutaneous melanoma. Altogether these findings suggest that the gene encoding AP-2α (TFAP2A) acts as a tumour suppressor in melanoma. To learn more of AP-2α's down-regulation mechanisms, we compared the immunohistochemical AP-2α protein expression patterns with the corresponding mRNA expression detected by in situ hybridization in 52 primary melanomas. Of the 25 samples with AP-2α protein negative areas, 16 (64%) expressed mRNA throughout the consecutive section. Nine specimens (36%) contained equally mRNA-and protein-negative areas, suggesting that the loss of AP-2α protein associated with lack of the mRNA transcript. The highly AP-2α protein-positive tumours (n = 27) were concordantly mRNA positive in 25 (92.6%) cases. Thirteen primary tumours were further analysed using microsatellite markers D6S470 and D6S263 for loss of heterozygosity (LOH) of a locus harbouring TFAP2A. LOHs or chromosome 6 monosomy were found in four out of five (80%) informative AP-2α mRNA-and protein-negative tumour areas, but also within five out of 13 (38%) informative AP-2α mRNA-positive tumour areas. This chromosome region is thus suggestive of harbouring a putative tumour suppressor gene of cutaneous melanoma, but this referring specifically to TFAP2A could not be completely verified in this analysis. We conclude that a failure in post-transcriptional processing of AP-2α is a possible inactivation mechanism of AP-2α in cutaneous melanoma.

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Molecular Pathology of Malignant Melanoma

Cited by 26 publications

References 46 publications

Clonal relationships between epidermotropic metastatic melanomas and their primary lesions: a loss of heterozygosity and X-chromosome inactivation-based analysis

Clonal relationships between epidermotropic metastatic melanomas and their primary lesions: a loss of heterozygosity and X-chromosome inactivation-based analysis

Cell adhesion and communication proteins are differentially expressed in melanoma progression model☆☆☆★

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