Annals of Oncology 13:1108-1115, 2002
© 2002 European Society for Medical Oncology
Original Paper |
p53 gene mutations are associated with poor survival in low and low-intermediate risk diffuse large B-cell lymphomas
1 Département de Pathologie, 2 Service d’Hématologie and 3 Unité d’Informatique Médicale, Hôpital Henri Mondor, AP-HP, Créteil; 4 Service d’Anatomie Pathologique and 9 Service d’Hématologie, Centre Hospitalier Lyon-Sud, Pierre-Bénite; 5 Service d’Anatomie Pathologique, Hôpitaux de Brabois, CHU Nancy; 6 Service d’Anatomie Pathologique and 10 Institut d’Hématologie, Hôpital Saint-Louis, AP-HP, Paris; 7 Service d’Anatomie Pathologique, Hôpital Dupuytren, Limoges; 8 Laboratoire de Génétique Oncologique, Centre Henri Becquerel, Rouen, France
Received 9 November 2001; revised 21 January 2002; accepted 12 February 2002
Background:
p53 alterations have been associated with a poor prognosis in aggressive B-cell lymphoma. We investigated the clinical relevance of p53 status in diffuse large B-cell lymphoma (DLBCL), focusing on patients who belong to lower risk groups of the international prognostic index and were uniformly treated. We aimed to determine whether this biological marker could identify among such patients those with a pejorative outcome who could benefit from a distinct therapeutic approach.
Patients and methods:
We studied 69 patients presenting with no, one (low-risk, n = 40) or two (low-intermediate risk, n = 29) risk factors treated with an anthracyclin-containing induction regimen. p53 exons 5–8 mutations were screened for using denaturing gradient gel electrophoresis and confirmed by direct sequencing. Immunohistochemical detection of p53 protein and of its downstream target p21 were also evaluated in 60 of 69 cases.
Results:
p53 mutations were detected in 16 of 69 (23%) lymphoma samples. The presence of a p53 gene mutation affected survival (P = 0.01), with a 6-year survival rate estimated to be 44% in mutated patients, compared with 79% in non-mutated ones. Using a stepwise Cox model, p53 mutation constituted the only parameter affecting survival (relative risk = 2.7, P = 0.03). A p53+/p21– immunohistochemical pattern (n = 15), suggestive of a disrupted p53 function, strongly correlated with p53 gene status and was associated with a lower 6-year survival rate when compared with a p53– or p53+/p21+ phenotype (47% versus 74%, P = 0.05).
Conclusions:
p53 alterations constitute a pejorative biological indicator able to discriminate among clinically defined lower risk patients with DLBCL.
Key words: diffuse large B-cell lymphomas, p53, survival
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