Pena J C, Thompson C B, Recant W, Vokes E E, Rudin C M
The Gwen Knapp Center for Lupus and Immunology Research, The Howard Hughes Medical Institute, University of Chicago, Illinois, USA.
Cancer. 1999 Jan 1;85(1):164-70. doi: 10.1002/(sici)1097-0142(19990101)85:1<164::aid-cncr23>3.0.co;2-q.
Inhibition of apoptosis, or programmed cell death, may be critical both in the development of cancer and in determining response to therapy. The authors examined the expression of two related apoptotic inhibitors, Bcl-2 and Bcl-xL, in pretreatment biopsies from a series of 42 patients with squamous cell carcinoma of the head and neck. The observed pattern of apoptotic inhibitor expression was compared with that of the p53 gene product, another factor implicated in carcinogenesis and therapeutic responsiveness.
Formalin fixed, paraffin embedded tumor biopsies from 42 patients with locally advanced squamous cell carcinoma of the head and neck were analyzed by immunohistochemistry using antibodies specific for Bcl-xL, Bcl-2, and p53. Measures of clinical outcome, including disease specific survival and overall survival, were compared among the groups.
The majority of the tumors demonstrated enhanced expression of either Bcl-2 or Bcl-xL compared with surrounding normal epithelium. Fifty-two percent of the tumors had up-regulated Bcl-xL, and 17% had up-regulated Bcl-2. There was no overlap between these groups. Expression of Bcl-2, but not Bcl-xL, was correlated with improved disease specific survival. Immunohistochemically detectable p53 expression (48% of tumors) was not found to correlate with expression of either Bcl-xL or Bcl-2 and, in this series, was not a predictor of clinical outcome.
These results suggest that disruption of apoptotic control pathways is an important event in the evolution of squamous cell carcinoma of the head and neck. A common mechanism for this disruption involves overexpression of Bcl-xL, Patients whose tumors demonstrate Bcl-2 positivity, even with locoregionally advanced disease, appear to have a high likelihood of cure with aggressive combined modality therapy and may be treated successfully with less toxic therapy.
细胞凋亡抑制，即程序性细胞死亡，在癌症发展及决定治疗反应方面可能都至关重要。作者检测了一系列42例头颈部鳞状细胞癌患者预处理活检组织中两种相关凋亡抑制因子Bcl-2和Bcl-xL的表达情况。将观察到的凋亡抑制因子表达模式与p53基因产物（另一个与致癌作用及治疗反应性有关的因子）的表达模式进行比较。
采用针对Bcl-xL、Bcl-2和p53的特异性抗体，通过免疫组织化学分析42例局部晚期头颈部鳞状细胞癌患者福尔马林固定、石蜡包埋的肿瘤活检组织。比较各亚组间包括疾病特异性生存和总生存在内的临床结局指标。
与周围正常上皮相比，大多数肿瘤显示Bcl-2或Bcl-xL表达增强。52%的肿瘤Bcl-xL上调，17%的肿瘤Bcl-2上调。这两组之间没有重叠。Bcl-2的表达而非Bcl-xL的表达与疾病特异性生存改善相关。免疫组织化学可检测到的p53表达（48%的肿瘤）与Bcl-xL或Bcl-2的表达均无相关性，在本系列研究中，它不是临床结局的预测指标。
这些结果表明，凋亡控制途径的破坏是头颈部鳞状细胞癌发生发展中的一个重要事件。这种破坏的一个常见机制是Bcl-xL的过表达。肿瘤显示Bcl-2阳性的患者，即使患有局部区域晚期疾病，似乎通过积极的综合治疗方式治愈的可能性很高，并且可能用毒性较小的治疗方法成功治疗。
