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 APC's 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.
authors.affiliation: Department of Cytopathology, University of Göttingen, Göttingen, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Korabiowska
authors.forename: Thilo
authors.initials: T
authors.lastname: Schlott
authors.forename: Nils
authors.initials: N
authors.lastname: Siems
authors.forename: Anegret
authors.initials: A
authors.lastname: Müller
authors.forename: Carlos
authors.initials: C
authors.lastname: Cordon-Cardo
authors.forename: Gösta
authors.initials: G
authors.lastname: Fischer
authors.forename: Ulrich
authors.initials: U
authors.lastname: Brinck
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000032:analysis / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D016019:Survival Analysis
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D004273:DNA, Neoplasm