Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Leuk Lymphoma. 2009 Oct;50(10):1597-605. doi: 10.1080/10428190903165241.
Although chromosome 17p abnormalities and TP53 mutations have been reported as poor prognostic indicators in chronic lymphocytic leukemia (CLL), the impact of aberrant p53 expression as assessed by immunohistochemistry (p53-IHC) has not been defined in patients with CLL treated with chemoimmunotherapy, particularly in the context of other novel markers such as ZAP-70 expression and IgVH mutation status (IgVH MS). We assessed p53-IHC in 222 bone marrow (BM) specimens from patients with CLL enrolled in a phase II trial with fludarabine, cyclophosphamide, and rituximab (FCR). ZAP70 expression and IgVH MS were assessed in 208 and 108 patients, respectively. One hundred sixty-eight patients had concurrent classical cytogenetic analysis. p53-IHC correlated with abnormal karyotype (p = 0.002) and adversely affected overall survival independent of ZAP70 expression and IgVH MS (p < 0.001). Patients with p53-IHC(+) CLL were less likely to achieve complete remission, but patients who did achieve complete remission showed a durable response. In this patient cohort, p53-IHC is an important determinant of complete remission and overall survival, but not remission duration, in patients with CLL receiving FCR.
虽然染色体 17p 异常和 TP53 突变已被报道为慢性淋巴细胞白血病 (CLL) 的不良预后指标，但在接受化疗免疫治疗的 CLL 患者中，免疫组织化学 (p53-IHC) 评估的异常 p53 表达的影响尚未确定，特别是在其他新型标志物（如 ZAP-70 表达和 IgVH 突变状态（IgVH MS））的背景下。我们评估了 222 例接受氟达拉滨、环磷酰胺和利妥昔单抗 (FCR) 治疗的 CLL 患者的骨髓 (BM) 标本中的 p53-IHC。在 208 例和 108 例患者中分别评估了 ZAP70 表达和 IgVH MS。168 例患者同时进行了经典细胞遗传学分析。p53-IHC 与异常核型相关（p = 0.002），并独立于 ZAP70 表达和 IgVH MS 对总生存产生不利影响（p < 0.001）。p53-IHC(+) CLL 患者更不可能达到完全缓解，但达到完全缓解的患者表现出持久的反应。在该患者队列中，p53-IHC 是接受 FCR 治疗的 CLL 患者完全缓解和总生存的重要决定因素，但不是缓解持续时间。
