title: DNA ploidy abnormalities in the liver of children with hereditary tyrosinemia type I. Correlation with histopathologic features.
abstract: Hereditary tyrosinemia (HT) is an autosomal recessive disorder of tyrosine metabolism that results in cirrhosis and hepatocellular carcinoma early in life, and that may be a useful model of early malignant transformation. This is the first report of DNA ploidy in this disease. The authors studied formalin-fixed liver tissue in three cases (two chronic and one acute) of HT for the presence of DNA aneuploidy by flow cytometric (FCM) analysis and image analysis (IA). In the chronic cases, the authors found DNA aneuploidy by FCM in 2/20 cirrhotic nodules in one case and 1/21 tissue sections in the other. Questionable minor aneuploid peaks were detected by FCM in 2/20 and 2/21 sections in these two cases, respectively. Static DNA measurements by IA were performed on those sections having abnormal histograms as well as in some sections having diploid DNA distribution. By this method, the authors confirmed the results of FCM studies and found additional small aneuploid nodules not detected by FCM, frequently associated with various forms of hepatocellular dysplasia as well as steatosis. In one case of acute HT (autopsy), no definite aneuploid peaks were present in five blocks. By immunohistochemical analysis, the authors found frequent positive staining for alpha-fetoprotein (AFP) in the cirrhotic nodules of the two chronic cases as well as in the steatotic regenerative nodules of the acute case. The expression of AFP may represent disturbed regeneration and maturation of liver cells in this disease. This study shows that DNA ploidy may be a useful marker for early malignant transformation in HT and supports the preneoplastic nature of the hepatocellular dysplasia in this disease.
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: C
authors.initials: C
authors.lastname: Zerbini
authors.forename: D S
authors.initials: DS
authors.lastname: Weinberg
authors.forename: K A
authors.initials: KA
authors.lastname: Hollister
authors.forename: A R
authors.initials: AR
authors.lastname: Perez-Atayde
mesh_terms: D002675:Child, Preschool; D002908:Chronic Disease; D004247:DNA / Q000235:genetics*; D005234:Fatty Liver / Q000473:pathology; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008103:Liver Cirrhosis / Q000503:physiopathology; D008661:Metabolism, Inborn Errors / Q000235:genetics* / Q000473:pathology; D011003:Ploidies; D012155:Reticulin / Q000378:metabolism; D014443:Tyrosine / Q000097:blood*; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D012155:Reticulin; D000509:alpha-Fetoproteins; D014443:Tyrosine; D004247:DNA