p53 gene mutations are uncommon but p53 is commonly expressed in anaplastic large-cell lymphoma.
Anaplastic large-cell lymphoma (ALCL), as defined in the World Health Organization, is a heterogeneous category in which a subset of cases is associated with the t(2;5)(p23;q35) or variant translocations resulting in overexpression of anaplastic lymphoma kinase (ALK). p53 has not been assessed in currently defined subsets of ALCL tumors. In this study, we assessed ALK+ and ALK- ALCL tumors for p53 gene alterations using PCR, single-strand conformation polymorphism and direct sequencing methods. We also immunohistochemically assessed ALCL tumors for p53 expression. Three of 36 (8%) ALCL tumors (1/14 ALK+, 2/22 ALK-) with adequate DNA showed p53 gene mutations. By contrast, p53 was overexpressed in 36 of 55 (65%) ALCL tumors (16 ALK+, 20 ALK-). p21, a target of p53, was expressed in 15 of 31 (48%) ALCL tumors including seven of 15 (47%) p53-positive tumors. p21 expression in a subset of ALCL suggests the presence of functional p53 protein. Apoptotic rate was significantly higher in p53-positive than p53-negative tumors (mean 2.78 vs 0.91%, P = 0.0003). We conclude that the p53 gene is rarely mutated in ALK+ and ALK- ALCL tumors. Nevertheless, wild-type p53 gene product is commonly overexpressed in ALCL and may be functional in a subset of these tumors.
Rassidakis
G Z
GZ
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Thomaides
A
A
Wang
S
S
Jiang
Y
Y
Fourtouna
A
A
Lai
R
R
Medeiros
L J
LJ
D000328:Adult; D000077548:Anaplastic Lymphoma Kinase; D017209:Apoptosis / Q000502:physiology; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics; D049109:Cell Proliferation; D003001:Cloning, Molecular; D050759:Cyclin-Dependent Kinase Inhibitor p21; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D051736:Proto-Oncogene Proteins c-mdm2; D020794:Receptor Protein-Tyrosine Kinases; D017422:Sequence Analysis, DNA / Q000379:methods; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics*
C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases