Apoptotic protein expression, glycogen content, DNA ploidy and cell proliferation in hepatoblastoma subtyping and their role in prognostication.
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.
Chopra
Anita
A
Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India.
Iyer
Venkateswaran K
VK
Agarwala
Sandeep
S
Mathur
Sandeep R
SR
Aron
Manju
M
Gupta
Siddharth Datta
SD
Verma
Kusum
K
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
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
Int J Cancer. 1997 Dec 19;74(6):593-9
9421354
J Pediatr Surg. 1997 Dec;32(12):1690-4
9434000
Semin Pediatr Surg. 2006 Feb;15(1):17-24
16458842
Cancer. 1991 Dec 15;68(12):2566-70
1657362
Cancer. 1993 Nov 15;72(10):2914-9
8221557
Acta Cytol. 2005 Jul-Aug;49(4):355-64
16124162
Liver. 1998 Apr;18(2):128-33
9588772
J Pediatr. 2005 Feb;146(2):204-11
15689909
J Pediatr Surg. 2001 May;36(5):755-9
11329582
Med Pediatr Oncol. 2002 Nov;39(5):478-83
12228903
Pediatr Surg Int. 2005 May;21(5):364-8
15838617
Anal Quant Cytol Histol. 1999 Dec;21(6):505-11
10626020