Expression of p53, p21, mdm2, Rb, bax and Ki67 proteins in lymphomas of the mucosa-associated lymphoid (MALT) tissue.
We have investigated by immunohistochemistry 38 cases of B-cell MALT-NHL comprising 23 high grade (HG) and 15 low grade-(LG) tumours for the expression of p53, mdm2, p21, Rb, Ki67, bcl2 and Bax proteins. P53, mdm2 and p21 proteins were found in at least 5% of the tumour cells in 13/23, 2/23 and 11/23 HG tumours, respectively. These proteins were detected in very rare tumour cells in LG tumours. The following patterns were recorded in HG tumours: p53+/p21+/mdm2+ (2 cases), p53+/p21+/mdm2- (7 cases), p53+/p21-/mdm2- (4 cases), p53-/p21-/mdm2- (18 cases) and p53-/p21+/mdm2-(2 cases). Proliferative Ki67 index and Rb protein expression were higher in HG than in LG MALT-NHL. Bcl2 protein was expressed in all LG MALT-NHL, whereas only 2/23 HG MALT-NHL were bcl2 positive in most tumour cells. Bax protein was expressed in all MALT-NHL with HG tumours being positive in higher proportion of tumour cells than LG tumours. These findings show that significant expression of p53, mdm2, p21,Ki67 and Rb proteins occurs more frequently in aggressive histotypes of MALT-NHL. The parallel Rb/Ki67 expression suggests that Rb protein expression in MALT-NHL is normally regulated in relation to the proliferative growth fraction of the tumours. The pattern p53+/p21+/mdm2 +/- may represent MALT-NHL with wild type (wt) p53 gene since mdm2 and p21 proteins are inducible by wt p53 gene. The pattern p53+/mdm2-/p21-may represent MALT-NHL with p53 gene mutations unable to activate expression of mdm2 and p21 proteins. MALT-NHL with the p53-/mdm2-/p21 + pattern may be consistent with p53-independent p21 expression. Bax protein expression in all MALT-NHL suggests a role for this protein in the pathogenesis of these tumours.
Department of Pathology, Medical School of Crete, Evangelismos Hospital, Athens, Greece.
K
K
Stefanaki
M
M
Tzardi
C
C
Kouvidou
V
V
Chaniotis
M
M
Bolioti
M
M
Vlychou
M
M
Zois
S
S
Kakolyris
G
G
Delides
D
D
Rontogianni
V
V
Georgoulias
P
P
Kanavaros
D002467:Cell Nucleus / Q000473:pathology; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000032:analysis*; D004791:Enzyme Inhibitors / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis*; D018442:Lymphoma, B-Cell, Marginal Zone / Q000473:pathology*; D009363:Neoplasm Proteins / Q000032:analysis; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D051736:Proto-Oncogene Proteins c-mdm2; D016160:Retinoblastoma Protein / Q000032:analysis*; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2