TY - JOUR
T1 - Constitutive activation of nuclear factor-kappa B (NF-κB) signaling pathway in fibrolamellar hepatocellular carcinoma
AU - Li, Wei
AU - Tan, Dongfeng
AU - Zenali, Maryam J.
AU - Brown, Robert E.
N1 - Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2010
Y1 - 2010
N2 - Fibrolamellar hepatocellular carcinoma (FLHCC) is an aggressive neoplasm due to high frequency of recurrence after surgical resection and resistance to chemotherapy and radiation therapy. Activation of transcription factor NF-κB signaling pathway has been recognized for involvement in progression of various malignant neoplasms. The role of NF-κB pathway in FLHCC has not been studied to date. Formalin-fixed, paraffin-embedded tissue sections of 8 FLHCC, 10 normal liver tissues (NLT) were evaluated immunohistochemically for the expression of p-NF-κBp65 using phosphospecific antibody directed against phosphorylated (p)-NF-κBp65 (Ser 536). The level of p-NF-κBp65 (Ser 536) expression was categorized into four grades: 0 (background), 1+ (weak), 2+ (moderate), or 3+ (strong) based on intensity of intranuclear staining, and was further assessed using two scales: high expression (2+ or 3+) and low expression (0 or 1+). Only high expression of p-NF-κBp65 (Ser 536) in cells with nuclear translocation was considered as constitutive NF-κB activation. High expression of p-NF-κBp65 (Ser 536) was found in 88 % (7/8) of FLHCC tissue. In contrast, only 10 % (1/10) of NLT showed high expression for p-NF-κBp65 (Ser 536). The differences in p-NF-κBp65 nuclear expression between FLHCC tissue and NLT were significant (P < 0.001). There was no significant correlation between the expression of intranuclear p-NF-κBp65 and the stage of FLHCC. Constitutive NF-κB activation was observed in FLHCC. The findings suggest that NF-κB activation is involved in the tumorigenesis of FLHCC and may represent novel targets for therapeutic intervention to FLHCC.
AB - Fibrolamellar hepatocellular carcinoma (FLHCC) is an aggressive neoplasm due to high frequency of recurrence after surgical resection and resistance to chemotherapy and radiation therapy. Activation of transcription factor NF-κB signaling pathway has been recognized for involvement in progression of various malignant neoplasms. The role of NF-κB pathway in FLHCC has not been studied to date. Formalin-fixed, paraffin-embedded tissue sections of 8 FLHCC, 10 normal liver tissues (NLT) were evaluated immunohistochemically for the expression of p-NF-κBp65 using phosphospecific antibody directed against phosphorylated (p)-NF-κBp65 (Ser 536). The level of p-NF-κBp65 (Ser 536) expression was categorized into four grades: 0 (background), 1+ (weak), 2+ (moderate), or 3+ (strong) based on intensity of intranuclear staining, and was further assessed using two scales: high expression (2+ or 3+) and low expression (0 or 1+). Only high expression of p-NF-κBp65 (Ser 536) in cells with nuclear translocation was considered as constitutive NF-κB activation. High expression of p-NF-κBp65 (Ser 536) was found in 88 % (7/8) of FLHCC tissue. In contrast, only 10 % (1/10) of NLT showed high expression for p-NF-κBp65 (Ser 536). The differences in p-NF-κBp65 nuclear expression between FLHCC tissue and NLT were significant (P < 0.001). There was no significant correlation between the expression of intranuclear p-NF-κBp65 and the stage of FLHCC. Constitutive NF-κB activation was observed in FLHCC. The findings suggest that NF-κB activation is involved in the tumorigenesis of FLHCC and may represent novel targets for therapeutic intervention to FLHCC.
KW - Fibrolamellar hepatocellular carcinoma
KW - Immunohistochemistry
KW - Nuclear factor-kappa B
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M3 - Article
C2 - 20224721
AN - SCOPUS:77953423408
SN - 1936-2625
VL - 3
SP - 238
EP - 243
JO - International journal of clinical and experimental pathology
JF - International journal of clinical and experimental pathology
IS - 3
ER -