DNA IMAGE CYTOMETRIC ANALYSIS OF MACROREGENERATIVE NODULES (ADENOMATOUS HYPERPLASIA) OF THE LIVER - EVIDENCE IN SUPPORT OF THEIR PRENEOPLASTIC NATURE

Twenty-eight macroregenerative nodules from 14 cirrhotic patients who underwent orthotopic liver transplantation were evaluated for DNA ploi dy by means of image analysis of Feulgen-stained tissue sections. The lesions were classified as type 1 (16 cases) or type 2 (12 cases) on t he basis of the absence or presence of cellular or architectural atypi a in the nodules. The surrounding cirrhotic nodules were evaluated for liver cell dysplasia. Aneuploid peaks were significantly more frequen t in type 2 macroregenerative nodules (58.3%) than in the cirrhotic re generative nodules (7.1%) (p < 0.007). In addition, aneuploid peaks oc curred with increased frequency in type 2 nodules (58.3%) than in type 1 macroregenerative nodules (6.2%) (p < 0.02). Only two aneuploid pea ks (14.2%) were found in dysplastic cirrhotic livers. The nuclear area of aneuploid hepatocytes (71.6 mum2 +/- 10. 1%, mean +/- S.D.) differ ed significantly from that of diploid liver cells (45.4 mum2 +/- 6.5%) (p < 0.0001). Tetraploid peaks occurred in three type 2 lesions (25%) ; they were also found in one type 1 macroregenerative nodule (6.2%), one cirrhotic liver without dysplasia (7.1%) and three cirrhotic liver s with dysplasia (21.4%). These findings support the notion that macro regenerative type 2 nodules are directly implicated in hepatocareinoge nesis and that their presence should be sought as an indicator of mali gnant potential in cirrhotic livers.