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 seve ral subtypes of non-Hodgkin's lymphoma, but the incidence of p53 mutat ions in mantle cell lymphoma (MCL) is unknown. We hypothesized that ca ses of MCL with a variant or high-grade cytology would have a higher l ikelihood of p53 mutations than typical MCL. We were also interested i n the prognostic significance of p53 mutations in MCL. Therefore, a se ries of 53 well-characterized cases of MCL with DNA from 62 tissue sam ples was analyzed by the polymerase chain reaction with denaturing gra dient gel electrophoresis for exons 5-8 of p53. Immunoperoxidase studi es 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 o ccurred 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), an d p53 mutations preceded the development of variant cytology in 2 pati ents. 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 med ian 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 year s (P = .023). These results suggest that mutations of p53 may be one m echanism involved in the development of variant forms of MCL and indic ate that p53 mutations in MCL predict a poor prognosis. (C) 1996 by Th e American Society of Hematology.