title: Heterogeneous topographic profiles of kinetic and cell cycle regulator microsatellites in atypical (dysplastic) melanocytic nevi.
abstract: Atypical (dysplastic) melanocytic nevi are clinically heterogeneous malignant melanoma precursors, for which no topographic analysis of cell kinetic, cell cycle regulators and microsatellite profile is available. We selected low-grade atypical melanocytic nevi (92), high-grade atypical melanocytic nevi (41), melanocytic nevi (18 junctional, 25 compound) and malignant melanomas (16 radial growth phase and 27 vertical growth phase). TP53, CDKN2A, CDKN1A, and CDKN1B microsatellite patterns were topographically studied after microdissection; Ki-67, TP53, CDKN2A, CDKN1A, and CDKN1B expressions and DNA fragmentation by in situ end labeling for apoptosis were topographically scored. Results were statistically analyzed. A decreasing junctional-dermal marker expression gradient was observed, directly correlating with atypical melanocytic nevus grading. High-grade atypical melanocytic nevi revealed coexistent TP53-CDKN2A-CDKN1B microsatellite abnormalities, and significantly higher junctional Ki67-TP53 expression (inversely correlated with CDKN1A-CDKN1B expression and in situ end labeling). Malignant melanomas showed coexistent microsatellite abnormalities (CDKN2A-CDKN1B), no topographic gradient, and significantly decreased expression. Melanocytic nevi and low-grade atypical melanocytic nevi revealed sporadic junctional CDKN2A microsatellite abnormalities and no significant topographic kinetic differences. High-grade atypical melanocytic nevi accumulate junctional TP53-CDKN1A-CDKN1B microsatellite abnormalities, being progression TP53-independent and better assessed in the dermis. Melanocytic nevi and low-grade atypical melanocytic nevi show low incidence of microsatellite abnormalities, and kinetic features that make progression unlikely.
authors.affiliation: Department of Histopathology, Barts and The London Hospitals, London, UK.
authors.forename: Ehab A
authors.initials: EA
authors.lastname: Husain
authors.forename: Charles
authors.initials: C
authors.lastname: Mein
authors.forename: Lucia
authors.initials: L
authors.lastname: Pozo
authors.forename: Alfredo
authors.initials: A
authors.lastname: Blanes
authors.forename: Salvador J
authors.initials: SJ
authors.lastname: Diaz-Cano
mesh_terms: D000328:Adult; D017209:Apoptosis; D018797:Cell Cycle Proteins / Q000032:analysis / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007700:Kinetics; D008131:London; D008297:Male; D042282:Microdissection; D018895:Microsatellite Repeats; D008875:Middle Aged; D009367:Neoplasm Staging; D009508:Nevus, Pigmented / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D013030:Spain; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: C493956:CDKN1A protein, human; C436291:CDKN1B protein, human; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D050760:Cyclin-Dependent Kinase Inhibitor p27