Bossard Céline, Belhadj Karim, Reyes Felix, Martin-Garcia Nadine, Berger Françoise, Kummer Jean Alain, Brière Josette, Baglin Anne-Catherine, Cheze Stéphane, Bosq Jacques, Ribrag Vincent, Gisselbrecht Christian, Mounier Nicolas, Gaulard Philippe
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.
Blood. 2007 Mar 1;109(5):2183-9. doi: 10.1182/blood-2006-07-033142. Epub 2006 Oct 31.
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.
鼻型NK/T细胞淋巴瘤是一种罕见的疾病实体，预后较差。抗凋亡蛋白的表达在该实体中尚未得到广泛研究。对48例接受一线多药化疗（n = 44）或放化疗（n = 4）的鼻型T/NK细胞淋巴瘤患者分析了活性半胱天冬酶-3（aC3）、颗粒酶B蛋白酶抑制剂9（PI9）和Bcl-2蛋白的表达。淋巴瘤为CD3+/CD5-/颗粒酶B+且与EB病毒相关。中位年龄为46岁。75%的病例为Ⅰ/Ⅱ期疾病，65%的病例国际预后指数（IPI）评分小于1。中位随访6.3年，5年无事件生存率（EFS）和总生存率（OS）分别为39%和49%。32%的病例凋亡指数评分高，68%的病例PI9表达为阳性，而35%的病例显示大量aC3+肿瘤细胞。单因素分析显示，PI9缺失和低凋亡指数与预后不良相关，但aC3表达和IPI评分无关。多因素分析显示，这两个参数分别独立影响EFS（P = 0.02和0.08）和OS（P = 0.009和0.04）。鉴于正常NK细胞的组成性表达，提示肿瘤细胞中PI9表达缺失可能反映了与疾病进展相关的某些机制。
