Expression of the granzyme B inhibitor PI9 predicts outcome in nasal NK/T-cell lymphoma: results of a Western series of 48 patients treated with first-line polychemotherapy within the Groupe d'Etude des Lymphomes de l'Adulte (GELA) trials
| Autor: | Nadine Martin-Garcia, Philippe Gaulard, Karim Belhadj, Nicolas Mounier, Stéphane Cheze, Jean Alain Kummer, Felix Reyes, Vincent Ribrag, Françoise Berger, Céline Bossard, Josette Brière, Anne-Catherine Baglin, Jacques Bosq, Christian Gisselbrecht |
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| Rok vydání: | 2006 |
| Předmět: |
Adult
Male medicine.medical_specialty Pathology T-Lymphocytes Immunology Nose Lymphoma T-Cell Biochemistry Gastroenterology Granzymes International Prognostic Index Internal medicine medicine Humans T-cell lymphoma Serpins Aged Univariate analysis Hematology business.industry Cell Biology Middle Aged Prognosis Natural killer T cell medicine.disease Lymphoma Killer Cells Natural Survival Rate Granzyme B Phenotype Treatment Outcome Drug Therapy Combination Female business Chemoradiotherapy |
| Zdroj: | Blood. 109:2183-2189 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2006-07-033142 |
| Popis: | Nasal NK/T-cell lymphoma is a rare disease entity with a poor outcome. Expression of antiapoptotic proteins has not been extensively investigated in this entity. Forty-eight patients with nasal T/NK-cell lymphoma who received first-line polychemotherapy (n = 44) or chemoradiotherapy (n = 4) were analyzed for expression of active caspase-3 (aC3), granzyme B protease inhibitor 9 (PI9), and Bcl-2 proteins. Lymphomas were CD3+/CD5−/granzyme B+ and EBV-associated. Median age was 46 years. Stage I/II disease was present in 75% of the cases and an International Prognostic Index (IPI) score less than 1 in 65%. With a median follow-up of 6.3 years, 5-year event-free survival (EFS) and overall survival (OS) rates were 39% and 49%, respectively. Apoptotic index was scored as high in 32% of cases and PI9 expression as positive in 68%, whereas 35% disclosed a high number of aC3+ tumor cells. Univariate analysis showed that absence of PI9 and low apoptotic index were associated with poor outcome, but not aC3 expression nor IPI score. By multivariate analysis, both parameters affected independently EFS (P = .02 and .08, respectively) and OS (P = .009 and .04). In view of its constitutive expression by normal NK cells, it is suggested that loss of PI9 expression in tumor cells may reflect some mechanism associated with progression. |
| Databáze: | OpenAIRE |
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