Levine E L, Renehan A, Gossiel R, Davidson S E, Roberts S A, Chadwick C, Wilks D P, Potten C S, Hendry J H, Hunter R D
Department of Experimental Radiation Oncology, Paterson Institute For Cancer Research, Manchester, UK.
Radiother Oncol. 1995 Oct;37(1):1-9. doi: 10.1016/0167-8140(95)01622-n.
Apoptosis is an important mechanism of cell death in tumours and it is seen both prior to and following radiotherapy. In this study patients with proven carcinoma of the cervix had measurement made of the percentage of apoptotic cells (apoptotic index or AI) in pre-therapy biopsies. Measurements of intrinsic radiosensitivity (SF2), already shown to be a predictor of outcome, had previously been made on the same pre-therapy biopsies. Mitotic index (MI) and Ki-67 antigen staining were also recorded as markers for proliferation. Patients were divided into those with an AI above or below the median and in general increasing apoptosis was associated with poor prognosis. The 5-year survival rate for tumours with an AI below the median was 79% and was significantly greater than the rate of 47% for those with an AI above the median (p = 0.003). There was also a significantly increased 5-year local recurrence-free rate for patients with an AI below the median compared with those with an AI above the median (79 versus 61%, p = 0.012). In addition, AI and SF2 acted as independent prognostic indicators. Patients with both an SF2 and AI value above the median did badly (25% 5-year survival, 46% local control) compared with those with an SF2 and AI below the median (80% 5-year survival, 100% local control). Apoptosis showed correlation with MI (n = 66, r = 0.34, p = 0.002) and cell staining for the Ki-67 antigen (n = 57, r = 0.25, p = 0.03), but neither MI nor Ki-67 were related to patient outcome. This suggests that while apoptosis may be a reflection of tumour proliferation this cannot in itself explain the ability of apoptosis to predict clinical outcome for this series of patients. The study raises the possibility of AI and SF2 being used together as predictors of tumour response to radiotherapy.
细胞凋亡是肿瘤细胞死亡的重要机制，在放疗前后均可观察到。在本研究中，对经证实患有宫颈癌的患者，在治疗前活检中测定凋亡细胞百分比（凋亡指数或AI）。此前已对相同的治疗前活检样本进行了内在放射敏感性（SF2）的测定，SF2已被证明是预后的预测指标。有丝分裂指数（MI）和Ki-67抗原染色也作为增殖标志物进行记录。患者被分为AI高于或低于中位数的两组，总体而言，凋亡增加与预后不良相关。AI低于中位数的肿瘤患者5年生存率为79%，显著高于AI高于中位数的患者的47%（p = 0.003）。与AI高于中位数的患者相比，AI低于中位数的患者5年局部无复发生存率也显著增加（79%对61%，p = 0.012）。此外，AI和SF2是独立的预后指标。与SF2和AI低于中位数的患者（5年生存率80%，局部控制率100%）相比，SF2和AI值均高于中位数的患者预后较差（5年生存率25%，局部控制率46%）。凋亡与MI（n = 66，r = 0.34，p = 0.002）和Ki-67抗原细胞染色相关（n = 57，r = 0.25，p = 0.03），但MI和Ki-67均与患者预后无关。这表明，虽然凋亡可能反映肿瘤增殖，但这本身并不能解释凋亡预测这组患者临床结局的能力。该研究提出了将AI和SF2一起用作肿瘤放疗反应预测指标的可能性。
