Dermal Analysis of CDKN1B (p27) Is the Most Useful Cell Cycle Regulator for Grading of Atypical Melanocytic Nevi
EA Husain, C Main, L Pozo, A Blanes, SJ Diaz-Cano. Barts and The London Hospital, London, United Kingdom; Homerton University Hospital, London, United Kingdom; University of Malaga School of Medicine, Malaga, Spain; King's College Hospital, London, United Kingdom
Background: Atypical (dysplastic) melanocytic nevi (AMN) are clinically heterogeneous malignant melanoma (MM) precursors. The value of cell kinetic, cell cycle regulators and microsatellite profile has not been assessed for AMN grading.
Design: We selected 133 lesions, classified into low-grade AMN (92), high-grade AMN (31), and MIS (10), according to standard criteria. Regular melanocytic nevi (15 junctional, 20 compound) and malignant melanomas (15 radial growth phase and 27 vertical growth phase) were used as controls. The microsatellite patterns of TP53, INK4a (p16), p21WAF1, and p27KIP1 were studied by PCR-capillary electrophoresis after topographic microdissection (junctional, superficial and deep dermal) and DNA extraction. The same areas were systematically studied for the expression of Ki-67, p53, p21WAF1, and p27Kip1, and scored by topographic compartments, screening the whole compartment in each case. The results (expressed as percentage of positive cells) were compared using analysis of variance and Student t-test, and considered significant if P<0.05. Results were statistically analyzed regarding grading (low vs. high) and topography (junctional vs. dermal).
Results: A decreasing junctional-dermal marker expression gradient was observed, showing statistically significant differences for TP53, RB1, CDKN2A and CDKN1B at the junction and CDKN1B at the dermis when comparing low-grade and high-grade AMN.
Statistically significant cell cycle regulators for AMN gradingAMN = Atypical melanocytic nevi, Junct = Junctional, Derm = Dermal
The microsatellite pattern showed coexistent TP53-CDKN2A-CDKN1B microsatellite abnormalities in high-grade AMN, with dermal TP53 and CDKN1B abnormalities. MM showed coexistent microsatellite abnormalities (CDKN2A-CDKN1B), with no topographic gradient and significantly decreased expression.
Conclusions: Although high-grade AMN accumulates junctional TP53-CDKN1A-CDKN1B microsatellite abnormalities, dermal microsatellite abnormalities for TP53 and CDKN1B are the most specific variables for grading AMN.
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 53, Wednesday Morning