鼻咽癌组织照射前后细胞凋亡的临床意义初探

Prognostic significance of apoptosis prior to and after different doses of radiotherapy in nasopharyngeal carcinoma: preliminary report

目的 采用末端脱氧核苷酸转移酶介导的脱氧核苷酸切口末端标记 (TUNEL)法检测鼻咽癌患者不同剂量照射前后肿瘤细胞凋亡的变化 ,并初步探讨其潜在的临床意义。方法 将接受根治性放射治疗的病理证实为鼻咽低分化鳞状细胞癌的 2 5例患者分为 5个组 ,每组 5例。 5个组分别在分割剂量 1.9Gy/次照射 1～ 5次后 3～ 6h活检取鼻咽肿瘤组织。采用TUNEL免疫组织化学法检测鼻咽癌组织放射治疗前、后肿瘤细胞凋亡。结果 放射治疗前、后凋亡指数均数分别为 0 .44(0 .10～ 1.15 ) ,0 .5 1(0 .0 5～ 1.40 ) (P >0 .0 5 )。照射 9.5Gy后的凋亡指数较放射治疗前明显增加(0 .98对 0 .44 ,P =0 .0 0 9)。凋亡指数 <0 .35和≥ 0 .35病例的无瘤生存率曲线差异无显著意义 (P >0 .0 5 )。影响无瘤生存率的单因素和多因素分析未显示出凋亡指数是独立的预后因素。结论 鼻咽癌常规分割照射 9.5Gy后肿瘤细胞凋亡指数较放射治疗前显著增加。放射治疗前肿瘤细胞自发性凋亡水平未显示出独立的预后价值。

Objective To evaluate the changes of tumor cell apoptosis prior to and after different doses of radiotherapy in patients with nasopharyngeal carcinoma (NPC) and to determine whether the frequency of apoptosis was correlated with prognosis. Methods Twenty five patients histologically proven to be nasopharyngeal squamous cell carcinoma were eligible to enter into this study. Patients were divided into 5 groups, 5 patients per group. Pretherapy biopsy and second biopsy from the nasopharyngeal tumor 3～6 hours after 1～5 fractions irradiation respectively (1.9?Gy per fraction a day) were taken. Apoptotic cells were identified and quantified by the terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) method. Results The mean of apoptotic index prior to and after radiotherapy were 0.44 (range: 0.10～1.15) and 0.51 (range:0.05～ 1.40 ) respectively (P>0.05). But the AI after 9.5?Gy in 5 fractions was significantly higher than that of pretherapy (0.98 versus 0.44, P=0.009). The disease free survival curve for patients with a low AI (<0.35) was not significantly different from that for those with a high AI (≥0.35), P>0.05. Univariate and multivariate analysis indicated that the AI of pretherapy biopsy showed no prognostic value. Conclusions The tumor cell AI after doses of 9.5?Gy in 5 fractions was higher than that of pretherapy for 25 patients with NPC in this study. Analysis with Cox regression models did not show the apoptotic index prior to treatment to be an independent prognostic factor.