Department of Radiotherapy, Democritus University of Thrace, Alexandroupolis, Greece.
Oncology. 2009;77(5):285-92. doi: 10.1159/000259260. Epub 2009 Nov 16.
We assessed the expression and the prognostic role of lactate dehydrogenase 5 (LDH5, the major LDH isoenzyme involved in anaerobic glycolysis) in patients with squamous cell head and neck cancer (SCHNC).
LDH5 was assessed immunohistochemically in whole tissue sections from 141 patients with SCHNC. Of these, 102 were subjected to surgery with (90 patients) or without (12 patients) postoperative radiotherapy (group A), while 39 patients were treated with radical radiotherapy (group B).
Mixed nuclear/cytoplasmic LDH5 expression was detected in 72.5% of group A and 61.5% of group B patients. This was significantly related to T4-stage (p = 0.04) and hypoxia-inducible factor-1alpha (HIF-1alpha) expression (p = 0.002). In group A, high LDH5 was linked with poorer distant metastasis-free survival (p = 0.01) and disease-specific overall survival (OS; p = 0.009). In multivariate analysis, LDH5 (p = 0.002) and HIF-1alpha (p = 0.01) were independently linked with distant metastasis. LDH5 was also linked with death events (p = 0.005). In group B, high LDH5 expression was significantly associated with poorer local relapse-free survival (p = 0.009) and OS (p = 0.01). In multivariate analysis, only T stage was a significant predictor of death events (p = 0.04).
LDH5 is highly expressed in SCHNC and is linked with local relapse, survival and distant metastasis, suggesting that LDH5 is a marker of radioresistance and a target for therapeutic interventions.
我们评估了乳酸脱氢酶 5(LDH5,主要的与无氧糖酵解有关的同工酶)在头颈部鳞状细胞癌(SCHNC)患者中的表达及其预后作用。
采用免疫组织化学方法检测 141 例 SCHNC 患者的整块组织切片中的 LDH5。其中,90 例接受了手术治疗,其中 90 例接受了术后放疗(A 组),12 例未接受术后放疗(A 组),39 例接受了根治性放疗(B 组)。
A 组和 B 组患者中分别有 72.5%和 61.5%的患者检测到混合核/浆 LDH5 表达。这与 T4 期(p=0.04)和缺氧诱导因子-1α(HIF-1α)表达(p=0.002)显著相关。在 A 组中,高 LDH5 与远处无转移生存(p=0.01)和疾病特异性总生存(OS;p=0.009)较差相关。多变量分析显示,LDH5(p=0.002)和 HIF-1α(p=0.01)与远处转移独立相关。LDH5 也与死亡事件相关(p=0.005)。在 B 组中,高 LDH5 表达与局部无复发生存(p=0.009)和 OS(p=0.01)较差显著相关。多变量分析显示,只有 T 分期是死亡事件的显著预测因素(p=0.04)。
LDH5 在 SCHNC 中高度表达,与局部复发、生存和远处转移相关,提示 LDH5 是放射抵抗的标志物,也是治疗干预的靶点。