存活素在鼻腔鼻窦恶性肿瘤中表达的临床意义

Expression of survivin in nasal and paranasal sinus carcinoma

目的探讨细胞凋亡抑制蛋白——存活素(survivin)在鼻腔鼻窦恶性肿瘤中的表达及其与肿瘤细胞自发性凋亡、患者临床病理参数和预后的关系,为临床筛选高危患者提供一定的参数。方法回顾性分析解放军总医院1991—2000年收治的48例原发性鼻腔鼻窦恶性肿瘤患者。所有患者均进行根治性手术,术后除4例患者未行放射治疗或化学治疗外,其余44例均行术后放疗,其中2例加行化疗。患者均随访3年以上,中位随访时间60·5个月。末端脱氧核苷酸转移酶介导的缺口末端标记法(terminaldeoxynucleotidyltransferase-mediateddUTPnickendlablling,TUNEL)结合碘化丙啶(propidiumiodide,PI)及HE染色检测肿瘤细胞自发性凋亡情况,过氧化物酶标记的链霉卵白素法(streptavidin-peroxidase-biotin,SP)检测存活素的表达。用Spearman相关进行存活素蛋白表达与凋亡指数的相关分析,采用Log-rank进行生存率的比较,采用Cox回归进行影响患者预后的多因素分析。结果48例中共有25例(52·08%)健在无肿瘤复发,3例(6·25%)肿瘤复发或远处转移带瘤生存,2例(4·17%)死于其他疾病,14例(29·17%)死于该病,4例(8·33%)失访,按死于该病局部复发计算。48例中23例(47·92%)肿瘤组织存活素表达阳性,阳性染色主要位于细胞质,呈颗粒状或棕黄色着色,偶有胞核着色,而癌旁正常组织未见表达。存活素阳性组的凋亡指数(2·2)低于阴性(0·7)组表达(P<0·05)。存活素阳性表达与凋亡指数呈负相关(r=-0·393,P=0·006)。晚期肿瘤(T3+T4)存活素表达高于早期肿瘤(T1+T2,χ2=3·944,P=0·047)。存活素阳性表达组总生存率明显低于阴性表达组(P<0·05)。多因素分析结果表明,存活素表达和肿瘤的组织学类型是影响患者预后的独立因素(P值分别为0·027和0·002)。结论存活素过度表达可能与鼻腔鼻窦恶性肿瘤的发生有关。存活素可能通过抑制肿瘤细胞凋亡参与肿瘤的发生和发展。临床检测存活素表达有助于筛选具有高复发和死亡风险性的鼻腔鼻窦恶性肿瘤患者。

Objective To assess the protein expression of a new inhibitor of apoptosis, survivin, and its correlation with spontaneous apoptosis, tumor clinicopathological parameters and prognosis in nasal and paranasal sinus carcinoma （NPSC）. Methods Forty-eight patients with NPSC treated by radical operations from 1991 to 2000 were studied retrospectively. Patients included 23 females and 25 males ranging in age from 20 to 71 years. Spontaneous apoptotic cells were visualized by TUNEL accompanied by HE and PI stain. Immunohistochemistry using SP method was used to assess the expression of survivin. Results Twenty-five patients （52. 08% ） survived without recurrence. Recurrence or metastasis occurred in 3 patients （6. 25% ）. Fourteen （29. 17% ） died from NPSC. Survivin expression was positive in 23 samples （23/48,47. 92% ）but no staining was present in normal tissues beside the tumors. The expression of survivin correlated negatively with the index of apoptosis （r = -0. 393, P =0. 006）. Patients with positive expression of survivin had lower apoptosis index than those with negative expression （P 〈0.05）. The expression of survivin in advanced stagetumors （T3 ＋ T4）was higher than early ones （T1 ＋ T2, P 〈 0. 05 ）. Patients with negative expression of survivin had much better prognosis than those with positive expression （P = 0. 0346 ）. Multivariate analyses revealed that expression of survivin and histological types were independent prognostic factors for overall survival. Conclusion An inverse correlation between survivin expression and the level of spontaneous apoptosis in NPSC suggests that survivin may play an important role in the tumorgenesis of NPSC. Survivin expression may provide a novel predictive indicator for disease-free survival after surgical resection and postoperative radiochemotheraov in NPSC.