title: Apoptotic protein expression, glycogen content, DNA ploidy and cell proliferation in hepatoblastoma subtyping and their role in prognostication.
abstract: OBJECTIVE
  To evaluate Bcl-xL, Bax, PCNA, cytokeratin 19 (CK-19), glycogen content and DNA ploidy expression in hepatoblastoma (HB) and their prognostic value.
  
  
  METHODS
  This retrospective study on 26 cases of HB involved DNA ploidy estimations separately for various subtypes on histological sections using image cytometry of Feulgen-stained smears. Glycogen content, PCNA, CK-19, Bax and Bcl-xL expression on tissue sections were evaluated. THE outcome on follow-up (mean 86 months) and Kaplan-Meier survival analysis were performed.
  
  
  RESULTS
  Fetal areas were diploid (84%); embryonal areas were aneuploid (89.47%) (p < 0.001). PCNA labeling index was low in fetal (10.82%) and high in embryonal areas (59.85%) (p = 0.03). CK-19 was negative in fetal, but focally positive in embryonal areas. Bax was negative in fetal (80%) and positive in embryonal areas (88.23%) (p < 0.001); Bcl-xL was more frequently positive in fetal (90%) than embryonal areas (52.94%) (p = 0.02). Fetal cells were rich in glycogen. Kaplan-Meier survival analysis showed good initial radiological response to chemotherapy (p = 0.009), glycogen content (p = 0.0137) and DNA diploid cases (p = 0.0429) were associated with good outcome on univariate analysis. Histology typing (p = 0.085), Bcl-xL (p = 0.689), Bax (p = 0.27), CK-19 (p = 0.281), PCNA (p = 0.689), age (p = 0.24), sex (p = 0.5661), stage (p = 0.24) and α-fetoprotein levels (p = 0.49) were unrelated to outcome. Multivariate analysis showed glycogen content to be the most statistically significant variable (0.024).
  
  
  CONCLUSIONS
  Fetal and embryonal areas show different staining patterns for PCNA, Bax and Bcl-xL. DNA ploidy and glycogen content are significant prognostic variables.
authors.affiliation: Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India.
authors.forename: Anita
authors.initials: A
authors.lastname: Chopra
authors.forename: Venkateswaran K
authors.initials: VK
authors.lastname: Iyer
authors.forename: Sandeep
authors.initials: S
authors.lastname: Agarwala
authors.forename: Sandeep R
authors.initials: SR
authors.lastname: Mathur
authors.forename: Manju
authors.initials: M
authors.lastname: Aron
authors.forename: Siddharth Datta
authors.initials: SD
authors.lastname: Gupta
authors.forename: Kusum
authors.initials: K
authors.lastname: Verma
mesh_terms: D000293:Adolescent; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D005260:Female; D006003:Glycogen / Q000378:metabolism; D018197:Hepatoblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007223:Infant; D053539:Keratin-19 / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D015999:Multivariate Analysis; D010503:Periodic Acid-Schiff Reaction; D011003:Ploidies; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016019:Survival Analysis; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: C494811:BCL2L1 protein, human; D014408:Biomarkers, Tumor; D053539:Keratin-19; D018809:Proliferating Cell Nuclear Antigen; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D006003:Glycogen
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