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Int J Clin Exp Pathol 2010;3(3):238-243
Original Article
Constitutive activation of nuclear factor-kappa B (NF-κB) signaling pathway in
fibrolamellar hepatocellular carcinoma
Wei Li, Dongfeng Tan, Maryam J Zenali, Robert E. Brown
Department of Pathology, University of Texas Health Science Center at Houston, Houston, TX, USA; Department of Pathology, University of
Texas, M.D. Anderson Cancer, Houston, TX, USA
Received December 16, 2009; accepted December 18, 2009; available online January 1, 2009
Abstract: 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. (IJCEP912005).
Key words: Fibrolamellar hepatocellular carcinoma, nuclear factor-kappa B, immunohistochemistry
Full text PDF
Address all correspondence to:
Wei Li, MD
Department of Pathology and Laboratory Medicine
University of Texas Health Science Center at Houston
6431 Fannin Street. MSB 2.278
Houston, TX 77030, USA Tel: 1-713- 500 – 5330
Fax: 1-713-500 – 0730
Email: Wei.Li@uth.tmc.edu
Original Article
Constitutive activation of nuclear factor-kappa B (NF-κB) signaling pathway in
fibrolamellar hepatocellular carcinoma
Wei Li, Dongfeng Tan, Maryam J Zenali, Robert E. Brown
Department of Pathology, University of Texas Health Science Center at Houston, Houston, TX, USA; Department of Pathology, University of
Texas, M.D. Anderson Cancer, Houston, TX, USA
Received December 16, 2009; accepted December 18, 2009; available online January 1, 2009
Abstract: 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. (IJCEP912005).
Key words: Fibrolamellar hepatocellular carcinoma, nuclear factor-kappa B, immunohistochemistry
Full text PDF
Address all correspondence to:
Wei Li, MD
Department of Pathology and Laboratory Medicine
University of Texas Health Science Center at Houston
6431 Fannin Street. MSB 2.278
Houston, TX 77030, USA Tel: 1-713- 500 – 5330
Fax: 1-713-500 – 0730
Email: Wei.Li@uth.tmc.edu
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