This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Møller, M. B. Articles by Pedersen, N. T. Search for Related Content PubMed PubMed Citation Articles by Møller, M. B. Articles by Pedersen, N. T.

Disrupted p53 Function as Predictor of Treatment Failure and Poor Prognosis in B- and T-Cell Non-Hodgkin’s Lymphoma¹

Departments of Pathology [M. B. M., N. T. P.], Clinical Genetics [A-M. G.], and Medical Microbiology [K. S.], Odense University, DK-5000 Odense, and Department of Medical Statistics, Danish Computing Centre for Research and Education, DK-8200 Aarhus [L. S. M.], Denmark

Mutation of the p53 gene has been associated with treatment failure and poor outcome in various malignancies. It has been suggested that immunohistochemical analysis of p53 and p21^Waf1, a downstream target, can be used to screen for p53 gene mutations. We determined the value of immunohistochemical screening for p53 gene mutations as a prognostic marker in a population-based group of B- and T-cell non-Hodgkin’s lymphomas (NHLs). On the basis of p53 gene mutation status and immunohistochemically detected p53 and p21^Waf1 expression in 34 lymphomas, we established an immunophenotype (p53) correlating with p53 gene mutation. The immunohistochemical analysis was extended to encompass 199 lymphomas from a population-based registry and was correlated with clinical parameters. p53 showed 100% concordance with p53 gene mutation and was detected in 42 cases (21%). Multivariate analysis of advanced stage lymphomas showed that p53 was independently associated with treatment failure (relative risk, 3.8; P = 0.001). p53 predicted poor survival when analyzing all patients (P = 0.0001), as well as B-cell (P = 0.04) and T-cell NHL (P = 0.000002). In multivariate analysis, p53 (relative risk, 2.2; P = 0.001) maintained prognostic significance. The impact on prognosis of p53 was highly significant in the low-intermediate-risk group (P = 0.00002). Comparing survival of the aggressive lymphoma patients in this group showed that the 8 p53 patients died within 1 year, whereas the median survival of the 28 non-p53 patients was 36 months. These results suggest that immunohistochemically assessed p53 status may predict treatment response and outcome in B- and T-cell NHL patients.

This article has been cited by other articles:

				K. H. Young, D. D. Weisenburger, B. J. Dave, L. Smith, W. Sanger, J. Iqbal, E. Campo, J. Delabie, R. D. Gascoyne, G. Ott, et al. Mutations in the DNA-binding codons of TP53, which are associated with decreased expression of TRAILreceptor-2, predict for poor survival in diffuse large B-cell lymphoma Blood, December 15, 2007; 110(13): 4396 - 4405. [Abstract] [Full Text] [PDF]

				M. A. Rizvi, A. M. Evens, M. S. Tallman, B. P. Nelson, and S. T. Rosen T-cell non-Hodgkin lymphoma Blood, February 15, 2006; 107(4): 1255 - 1264. [Abstract] [Full Text] [PDF]

				M. Sanchez-Beato, A. Sanchez-Aguilera, and M. A. Piris Cell cycle deregulation in B-cell lymphomas Blood, February 15, 2003; 101(4): 1220 - 1235. [Abstract] [Full Text] [PDF]

				U. Gianelli, C. Patriarca, A. Moro, M. Ponzoni, R. Giardini, M. Massimino, R. M. Alfano, E. Armiraglio, P. Nuciforo, S. Bosari, et al. Lymphomas of the Bone: A Pathological and Clinical Study of 54 Cases International Journal of Surgical Pathology, October 1, 2002; 10(4): 257 - 266. [Abstract] [PDF]

				K. Leroy, C. Haioun, E. Lepage, N. Le Metayer, F. Berger, E. Labouyrie, V. Meignin, B. Petit, C. Bastard, G. Salles, et al. p53 gene mutations are associated with poor survival in low and low-intermediate risk diffuse large B-cell lymphomas Ann. Onc., July 1, 2002; 13(7): 1108 - 1115. [Abstract] [Full Text] [PDF]

				S. L. Barrans, I. Carter, R. G. Owen, F. E. Davies, R. D. Patmore, A. P. Haynes, G. J. Morgan, and A. S. Jack Germinal center phenotype and bcl-2 expression combined with the International Prognostic Index improves patient risk stratification in diffuse large B-cell lymphoma Blood, February 15, 2002; 99(4): 1136 - 1143. [Abstract] [Full Text] [PDF]

				A. M. Gruszka-Westwood, R. A. Hamoudi, E. Matutes, E. Tuset, and D. Catovsky p53 abnormalities in splenic lymphoma with villous lymphocytes Blood, June 1, 2001; 97(11): 3552 - 3558. [Abstract] [Full Text] [PDF]

				M. Filipits, U. Jaeger, I. Simonitsch, C. Chizzali-Bonfadin, H. Heinzl, and R. Pirker Clinical Relevance of the Lung Resistance Protein in Diffuse Large B-Cell Lymphomas Clin. Cancer Res., September 1, 2000; 6(9): 3417 - 3423. [Abstract] [Full Text]

				C.A. SCHMITT, R.R. WALLACE-BRODEUR, C.T. ROSENTHAL, M.E. MCCURRACH, and S.W. LOWE DNA Damage Responses and Chemosensitivity in the E{micro}-myc Mouse Lymphoma Model Cold Spring Harb Symp Quant Biol, January 1, 2000; 65(0): 499 - 510. [Abstract] [PDF]