Analysis of adenomatous polyposis coli gene expression, APC locus-microsatellite instability and APC promoter methylation in the progression of melanocytic tumours Journal Article


Authors: Korabiowska, M.; Schlott, T.; Siems, N.; Müller, A.; Cordon-Cardo, C.; Fischer, G.; Brinck, U.
Article Title: Analysis of adenomatous polyposis coli gene expression, APC locus-microsatellite instability and APC promoter methylation in the progression of melanocytic tumours
Abstract: Adenomatous polyposis coli gene (APC) defects have been demonstrated for the first time in familial adenomatous polyposis. Recent reports indicate that the APC gene is an intermediary between cell adhesion molecules and the cytoskeleton and that it may function as a gatekeeper of colonic epithelial proliferation. The objective of this study was to analyse APCs presence in lentigos, primary melanomas and melanoma metastases. By immunohistochemistry, APC was demonstrated in all lentigos, in 75 out of 88 primary melanomas and in 16 out of 28 melanoma lymphatic metastases. The percentage of immunolabelled tumour cells (APC index) in lentigos ranged between 5 and 69%, in primary melanomas between 0 and 98% and in melanoma metastases between 0 and 52%. Statistically significant differences between lentigos and primary melanomas and between lentigos and metastases in APC expression were found. In a multivariate analysis, APC showed an independent prognostic impact. Analysis of microsatellite instability in the APC locus was performed on 29 melanomas. Microsatellite instability was found in 5/29 melanomas and loss of heterozygosity in 1/29 melanomas. Promoter methylation of APC was found in 6/10 APC-negative primary melanomas and in 9/10 APC-negative melanoma lymphatic metastases investigated. We conclude about important role of APC alterations for melanoma progression.
Keywords: immunohistochemistry; adult; human tissue; aged; aged, 80 and over; middle aged; survival analysis; major clinical study; methylation; promoter region; cancer growth; lymph node metastasis; lymphatic metastasis; cell proliferation; gene; melanoma; metastasis; gene expression; gene locus; dna methylation; microsatellite instability; dna, neoplasm; multivariate analysis; heterozygosity loss; loss of heterozygosity; cell adhesion; cytoskeleton; adenomatous polyposis coli protein; microsatellite repeats; promoter methylation; colon mucosa; antibody labeling; lentigo; apc; promoter regions (genetics); adenomatous polyposis coli gene; humans; prognosis; human; male; female; priority journal; article
Journal Title: Modern Pathology
Volume: 17
Issue: 12
ISSN: 0893-3952
Publisher: Nature Research  
Date Published: 2004-12-01
Start Page: 1539
End Page: 1544
Language: English
DOI: 10.1038/modpathol.3800238
PROVIDER: scopus
PUBMED: 15257316
DOI/URL:
Notes: Mod. Pathol. -- Cited By (since 1996):11 -- Export Date: 16 June 2014 -- CODEN: MODPE -- Source: Scopus
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