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Int J Clin Exp Pathol 2010;3(3):244-253
Original Article
Biological and clinical significance of GSK-3β in mantle cell lymphoma–an
immunohistochemical study
Randy Chung, Anthea C Peters, Hanan Armanious, Mona Anand, Pascal Gelebart, Raymond Lai
From the 1Department of Medicine, University of Alberta; 2the Department of Laboratory Medicine & Pathology, Cross Cancer Institute and
University of Alberta, Edmonton, Alberta, Canada.
Received January 19, 2010; accepted January 22, 2010; available online January 25, 2009.
Abstract: GSK-3β, a biologically important signalling protein, is regulated by the Wnt canonical and the PI3K/Akt pathways. We recently reported
that mantle cell lymphoma (MCL) frequently shows evidence of GSK-3β inactivation, since GSK-3β is phoshorylated at its functionally critical
serine 9 residue in all MCL cell lines and the majority of MCL tumors examined. To further assess the clinical and biological significance of
GSK-3β inactivation in MCL, we employed immunohistochemistry to assess the expression of the phosphorylated/inactive form of GSK-3β
(pGSK-3β) in 83 paraffin-embedded tumors, and correlated its expression with various biological and clinical parameters. Dichotomizing pGSK-
3β into 2 groups produced twenty-seven (32.5%) tumors assessed as negative and fifty-six (67.5%) as positive. Positive pGSK-3β expression
correlated significantly with positive nuclear expression of β-catenin and high expression of cyclin D1 (p = 0.0025, 0.0032 Fisher’s exact,
respectively), both of which have been previously shown to be regulated by GSK-3β regarding their expression levels and/or sub cellular
localization in-vitro. However, no significant correlation was found between pGSK-3β and Ki67. Of the clinical parameters, continuous pGSK-3β
status had a significant correlation with absolute lymphocyte count in blood (p = 0.0011, Spearman) and negative pGSK-3β expression was
significantly correlated with a longer overall survival (p= 0.045, HR = 1.89), but not with age at diagnosis, clinical stage or the international
prognostic index. To conclude, our results support the concept that GSK-3β inactivation, found in approximately two-thirds of MCL tumors, is
biologically and clinically important in MCL. (IJCEP1001006).
Key words: Mantle cell lymphoma, GSK-3β, immunohistochemistry
Full text PDF
Address all correspondence to:
Raymond Lai, MD, PhD
Department of Laboratory Medicine and Pathology
Cross Cancer Institute and University of Alberta
11560 University Avenue
Edmonton, Alberta
Canada T6G 1Z2, Tel: 780-432-8338; Fax: 780-432-8214
E-mail: rlai@ualberta.ca
Original Article
Biological and clinical significance of GSK-3β in mantle cell lymphoma–an
immunohistochemical study
Randy Chung, Anthea C Peters, Hanan Armanious, Mona Anand, Pascal Gelebart, Raymond Lai
From the 1Department of Medicine, University of Alberta; 2the Department of Laboratory Medicine & Pathology, Cross Cancer Institute and
University of Alberta, Edmonton, Alberta, Canada.
Received January 19, 2010; accepted January 22, 2010; available online January 25, 2009.
Abstract: GSK-3β, a biologically important signalling protein, is regulated by the Wnt canonical and the PI3K/Akt pathways. We recently reported
that mantle cell lymphoma (MCL) frequently shows evidence of GSK-3β inactivation, since GSK-3β is phoshorylated at its functionally critical
serine 9 residue in all MCL cell lines and the majority of MCL tumors examined. To further assess the clinical and biological significance of
GSK-3β inactivation in MCL, we employed immunohistochemistry to assess the expression of the phosphorylated/inactive form of GSK-3β
(pGSK-3β) in 83 paraffin-embedded tumors, and correlated its expression with various biological and clinical parameters. Dichotomizing pGSK-
3β into 2 groups produced twenty-seven (32.5%) tumors assessed as negative and fifty-six (67.5%) as positive. Positive pGSK-3β expression
correlated significantly with positive nuclear expression of β-catenin and high expression of cyclin D1 (p = 0.0025, 0.0032 Fisher’s exact,
respectively), both of which have been previously shown to be regulated by GSK-3β regarding their expression levels and/or sub cellular
localization in-vitro. However, no significant correlation was found between pGSK-3β and Ki67. Of the clinical parameters, continuous pGSK-3β
status had a significant correlation with absolute lymphocyte count in blood (p = 0.0011, Spearman) and negative pGSK-3β expression was
significantly correlated with a longer overall survival (p= 0.045, HR = 1.89), but not with age at diagnosis, clinical stage or the international
prognostic index. To conclude, our results support the concept that GSK-3β inactivation, found in approximately two-thirds of MCL tumors, is
biologically and clinically important in MCL. (IJCEP1001006).
Key words: Mantle cell lymphoma, GSK-3β, immunohistochemistry
Full text PDF
Address all correspondence to:
Raymond Lai, MD, PhD
Department of Laboratory Medicine and Pathology
Cross Cancer Institute and University of Alberta
11560 University Avenue
Edmonton, Alberta
Canada T6G 1Z2, Tel: 780-432-8338; Fax: 780-432-8214
E-mail: rlai@ualberta.ca
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