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.
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.
Bossard
Céline
C
Département de Pathologie and Institut National de la Santé et de la Recherche Médicale (Inserm) Unité (U) 617, Hôpital Henri Mondor, Assistance Publique-Hôpitaux de Paris (AP-HP), Créteil, France.
Belhadj
Karim
K
Reyes
Felix
F
Martin-Garcia
Nadine
N
Berger
Françoise
F
Kummer
Jean Alain
JA
Brière
Josette
J
Baglin
Anne-Catherine
AC
Cheze
Stéphane
S
Bosq
Jacques
J
Ribrag
Vincent
V
Gisselbrecht
Christian
C
Mounier
Nicolas
N
Gaulard
Philippe
P
D000328:Adult; D000368:Aged; D004359:Drug Therapy, Combination; D005260:Female; D053804:Granzymes / Q000037:antagonists & inhibitors*; D006801:Humans; D007694:Killer Cells, Natural / Q000187:drug effects / Q000201:enzymology*; D016399:Lymphoma, T-Cell / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009666:Nose / Q000276:immunology / Q000473:pathology; D010641:Phenotype; D011379:Prognosis; D015843:Serpins / Q000378:metabolism*; D015996:Survival Rate; D013601:T-Lymphocytes / Q000187:drug effects / Q000201:enzymology*; D016896:Treatment Outcome
C102316:SERPINB9 protein, human; D015843:Serpins; D053804:Granzymes