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Journal of Clinical Oncology, Vol 23, No 13 (May 1), 2005: pp. 3158-3159 © 2005 American Society of Clinical Oncology. DOI: 10.1200/JCO.2005.05.159
p53 Expression As a Prognostic Indicator in Hodgkin's LymphomaHematology and Pathology Departments, School of Medicine, Federal University of Rio de Janeiro, Rio de Janiero, Brazil To the Editor: We have read with great interest the report by the Spanish Hodgkin's Lymphoma Group (SHLG) about the influence of biologic markers on the outcome of Hodgkin's lymphoma (HL).1 The authors concluded that the concomitant evaluation of p53, Bcl-XL and TUNEL can help to improve the prognostic discrimination in patients in the low-risk group according to the International Prognostic Score. We congratulate the authors for the nice work, but we believe further remarks are warranted on the prognostic role of p53 in HL. The authors limit their discussion regarding p53 to citing three articles in which they say p53 expression was found to have an adverse effect on the overall survival or the disease-free survival.2-4 One of these three papers, however, is the group's own series of 288 patients reported last year in Blood.2 The authors acknowledge that "some" of these patients have been included again in this report, but do not give the exact proportion. Yet, it is puzzling to observe that, while the positivity thresholds used were the same in both studies, the proportion of p53-positive cases has risen from 15.5% to 29.5%. A careful reading of another of these three papers3 will establish quite a different conclusion. No significant differences were found in the univariate analysis of the impact of p53 expression on the overall survival (P = .34). Moreover, the data suggested that a high p53 expression is a predictor of a more favorable outcome, not of a worse outcome as cited by Montalbán et al. On the other hand, the authors failed to mention two other studies in which p53 was found to have no influence on outcome.5,6 One of these studies, surprisingly, was also conducted by the SHLG, and included 210 patients, presumably not included in the later studies.6 This negative finding is in agreement with our own experience with 86 patients with HL, 74% of whom were found to be positive for p53 at the 10% threshold. There were no statistically significant differences in the complete remission rate, failure-free survival, or overall survival according to p53 expression. These discordant results might reflect, at least in part, the wide variation in the positivity criteria used in these studies. Positivity thresholds varied from > 10% to > 80%, while the proportion of positive cases seemed to be inversely proportional to the positivity threshold, and varied from 93% to 30%. There is an urgent need for standardization of these definitions, as well as of the methodology used by examiners in cell counting, if these methods are ever to influence clinical decisions. In summary, the available evidence is quite controversial, and it is uncertain whether p53 expression can be used as an additional prognostic indicator in HL. Authors' Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest. REFERENCES
1. Montalbán C, Garcia JF, Abraira V, et al: Influence of biologic markers on the outcome of Hodgkin's lymphoma: A study by the Spanish Hodgkin's Lymphoma Study Group. J Clin Oncol 22:1664-1673, 2004
2. Garcia JF, Camacho FI, Morente M, et al: Hodgkin and Reed-Sternberg cells harbor alterations in the major tumor suppressor pathways and cell-cycle checkpoints: Analyses using tissue microarrays. Blood 101:681-689, 2003 3. Brink AA, Oudejans JJ, van den Brule AJ, et al: Low p53 and high bcl-2 expression in Reed-Sternberg cells predicts poor clinical outcome for Hodgkin's disease: Involvement of apoptosis resistance? Mod Pathol 11:376-383, 1998[Medline]
4. Smolewski P, Robak T, Krykowski E, et al: Prognostic factors in Hodgkin's disease: Multivariate analysis of 327 patients from a single institution. Clin Cancer Res 6:1150-1160, 2000 5. Xerri L, Bouabdallah R, Camerlo J, et al: Expression of the p53 gene in Hodgkin's disease: Dissociation between immunohistochemistry and clinicopathological data. Hum Pathol 25:449-454, 1994[CrossRef][Medline]
6. Morente MM, Piris MA, Abraira V, et al: Adverse clinical outcome in Hodgkin's disease is associated with loss of retinoblastoma protein expression, high Ki67 proliferation index, and absence of Epstein-Barr virus-latent membrane protein 1 expression. Blood 90:2429-2436, 1997
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Copyright © 2005 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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