Cell kinetic contributions to the genetic heterogeneity of C-cell hyperplasias (CCH) and adrenal medullary hyperplasias (AMH) in multiple endocrine neoplasia 2A remain unknown.Methods: We selected 22 CCH foci and 34 AMH nodules from MEN-2A kindred (RET mutation in codon 634). DNA extracted from microdissected samples was used for microsatellite analysis of TP53, RB1, WT1, and NF1 by PCR-denaturing gradient gel electrophoresis. Ki-67, in situ end labeling (ISEL), and kinetic (Ki-67/1SEL) indices

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... were calculated in each sample. Only informative cases were included.Results: CCH revealed higher and more homogeneous incidence of loss of heterozygosity (LOH) for [ TP53 (I 2120, 60%), and R67 (8114, 57%)1 than AMH [TP53 (9/31,29%), RBI (3125, 12%), WTI (9128, 32%), and NF7 (9119, 47%)]. Coexistent LOH in $2 loci were observed in 5/20 CCH and 6/31 AMH, always involving TP53 in CCH and NF7 in AMH. Kinetic indices were significantly higher in lesions accumulating multiple LOH than in lesions with single LOH (261.25 VS. 169.38), due to decreased ISEL indices.Conclusions: MEN 2A lesions accumulating somatic genetic abnormalities reveal the most advantageous kinetic profile essentially due to down-regulated apoptois. Differential genetic profile contributes to that pattern, involving TP53/RB1 in CCH and NF1 in AMH.