p53 mutations in mantle cell lymphoma are associated with variant cytology and predict a poor prognosis.
Mutations of the p53 tumor suppressor gene have been described in several subtypes of non-Hodgkin's lymphoma, but the incidence of p53 mutations in mantle cell lymphoma (MCL) is unknown. We hypothesized that cases of MCL with a variant or high-grade cytology would have a higher likelihood of p53 mutations than typical MCL. We were also interested in the prognostic significance of p53 mutations in MCL. Therefore, a series of 53 well-characterized cases of MCL with DNA from 62 tissue samples were analyzed by the polymerase chain reaction with denaturing gradient gel electrophoresis for exons 5-8 of p53. Immunoperoxidase studies with the antibody DO-7 to p53 protein were also performed on frozen sections. We found mutations of the p53 gene in 8 of the 53 cases (15%) of MCL. Missense mutations predominated, and 50% of the mutations occurred at known p53 hotspot codons. Of 21 cases with variant cytology (ie, anaplastic or blastic), 6 (28.6%) had p53 mutations as compared with only 2 of 32 cases (6.3%) with typical MCL cytology (P = .05), and p53 mutations preceded the development of variant cytology in 2 patients. Overexpression of p53 protein was observed in 6 of the 8 cases (75%) with p53 mutations and in none of the 45 wild-type cases. The median survival of the cases with mutant p53 was only 1.3 years (all died), whereas the median survival of cases with germline p53 was 5.1 years (P = .023). These results suggest that mutations of p53 may be one mechanism involved in the development of variant forms of MCL and indicate that p53 mutations in MCL predict a poor prognosis.
Greiner
T C
TC
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha 68198-3135, USA.
Moynihan
M J
MJ
Chan
W C
WC
Lytle
D M
DM
Pedersen
A
A
Anderson
J R
JR
Weisenburger
D D
DD
D001483:Base Sequence; D004273:DNA, Neoplasm / Q000235:genetics; D005091:Exons / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000096:biosynthesis; D016133:Polymerase Chain Reaction; D011379:Prognosis; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53