title: Hepatoblastoma: DNA nuclear content, proliferative indices, and pathology.
abstract: Hepatoblastoma (HB) is the most frequent malignant liver tumor in infancy, and both its biological features and its prognostic behavior are still under investigation. DNA content and proliferative activity of the tumor have been considered as biological parameters related to the tumor's aggressiveness. The present study attempts to investigate the possible association between histologic subtype, DNA content, and proliferative indices in HB. DNA content and the proportion of cells in the S-phase were assessed by flow cytometry in 34 cases of HB (14 prior to chemotherapy, 20 after chemotherapy), using formalin-fixed, paraffin-embedded archival samples. The proliferative cell nuclear antigen (PCNA) labeling index was also evaluated by immunohistochemistry, and both the flow cytometry (FC) and the immunohistochemical data were correlated with tumor pathology. A significant association was found between histological type, DNA content and the percentage of cells in the S-phase, with aneuploidy and the highest proportions of S-phase cells significantly associated with embryonal tumors. The PCNA labeling index was found to be significantly higher in embryonal than in fetal phenotype. The biological heterogeneity of HB is Confirmed by the different nuclear content of the fetal (diploid) and embryonal (aneuploid) epithelial components of the tumor, also ruling out the likelihood of fetal (diploid) clones deriving from the embryonal (aneuploid) neoplastic cells. Since the highly proliferative neoplastic clones (i.e., embryonal) are thought to be more sensitive to antimitotic drugs, further studies are indicated to determine the relationship between ploidy, proliferative indices and chemoresponsiveness.
authors.affiliation: Istituto di Anatomia Patologica, Cattedra di Istochimica & Immunoistochimica Patologica, Università di Padova, Veneto, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Rugge
authors.forename: F
authors.initials: F
authors.lastname: Sonego
authors.forename: L
authors.initials: L
authors.lastname: Pollice
authors.forename: G
authors.initials: G
authors.lastname: Perilongo
authors.forename: M
authors.initials: M
authors.lastname: Guido
authors.forename: G
authors.initials: G
authors.lastname: Basso
authors.forename: V
authors.initials: V
authors.lastname: Ninfo
authors.forename: N
authors.initials: N
authors.lastname: Pennelli
authors.forename: C
authors.initials: C
authors.lastname: Gambini
authors.forename: M
authors.initials: M
authors.lastname: Guglielmi
authors.forename: A
authors.initials: A
authors.lastname: Fabiano
authors.forename: G
authors.initials: G
authors.lastname: Leandro
authors.forename: J W
authors.initials: JW
authors.lastname: Keeling
mesh_terms: D002648:Child; D002675:Child, Preschool; D004273:DNA, Neoplasm / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D018197:Hepatoblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008940:Mitotic Index; D011003:Ploidies; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012372:ROC Curve; D016196:S Phase
chemical_list: D004273:DNA, Neoplasm; D018809:Proliferating Cell Nuclear Antigen